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Real-World Data on Prognostic Factors for Overall Survival in EGFR-Mutant Non-Small-Cell Lung Cancer Patients with Brain Metastases
Xiaoqing Yu1, Yun Fan1,2
1. Department of Thoracic Medical Oncology, Zhejiang Caner Hospital, Hangzhou, 310022, Zhejiang, People's Republic of China
2. Key laboratory Diagnosis and Treatment Technology on Thoracic Oncology (esophagus, lung), Zhejiang Caner Hospital, 310022, Zhejiang, People's Republic of China
✉ Corresponding author: Dr. Yun Fan, Department of Thoracic Medical Oncology; Key laboratory Diagnosis and Treatment Technology on Thoracic Oncology (esophagus, lung), Zhejiang Caner Hospital, No 1, East Banshan Road, Gongshu District, Hangzhou, 310022, Zhejiang, People's Republic of China. Fax +86 571 8812 2589. Email: fanyun_zjcccom More
Yu X, Fan Y. Real-World Data on Prognostic Factors for Overall Survival in EGFR-Mutant Non-Small-Cell Lung Cancer Patients with Brain Metastases. J Cancer 2019; 10(15):3486-3493. doi:10.7150/jca.30292. Available from https://www.jcancer.org/v10p3486.htm
Background: With the wide application of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), the survival of EGFR-mutant non-small-cell lung cancer (NSCLC) patients with brain metastasis (BM) has been significantly improved. However, prognosis analysis for patients with EGFR mutation and BM is still lacking, and the prognostic factors remain to be determined.
Materials and methods: A total of 746 NSCLC patients with BM were identified between January 2013 and December 2016 at our institution. Overall, 261 patients harboring EGFR mutation and meeting the inclusion criteria for the study were enrolled. Exclusion criteria included KPS<50, diagnosed with BM during treatment with EGFR-TKIs, or insufficient follow-up. Overall survival (OS) was measured from the date of brain metastases. Independent prognostic factors were confirmed using a Cox regression model.
Results: The median follow-up time for these patients was 32.7 months (95% CI, 23.5-41.9). The median OS after development of brain metastases was 23.0 months (95% CI, 20.01-25.99). By univariate analysis, significantly shorter OS was noted in patients older than 65 years (p=0.025), KPS <70 (p=0.003), presence of extracranial metastases (ECM) (p=0.00), without intracranial local treatment (p=0.000), and without chemotherapy (p=0.001). There was no difference in OS with respect to EGFR mutation type and number of BM (p=0.343, p=0.729, respectively). The Cox proportional hazards regression model revealed that performance status (KPS<70, p=0.010), ECM (p=0.001), receiving intracranial local treatment (p=0.005) and chemotherapy (p=0.005) were independent prognostic factors for OS, while age was not (p=0.087). Patients with higher diagnosis-specific graded prognostic assessment (DS-GPA) and Lung-molGPA scores corresponded to better prognosis (p=0.000).
Conclusion: This retrospective analysis demonstrated that performance status (KPS≥70), absence of ECM metastases, administration of local treatment and chemotherapy were associated with superior OS in patients with EGFR-mutant NSCLC who developed BM. The DS-GPA and Lung-molGPA indexes still applied to NSCLC patients with mutant genotypes and BM.
Keywords: Non-Small-Cell Lung Cancer, Brain Metastases, Prognostic Factors, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Brain metastasis (BM) has become a leading cause of death from non-small-cell lung cancer (NSCLC), with an incidence of approximately 25-40% [1, 2]. As systemic therapies improve, NSCLC patients live longer and are thus at an increased risk for brain metastases. For patients harboring epidermal growth factor receptor (EGFR) mutations, the incidence of BM is up to 50%, which seriously affects patient prognosis [3]. The reported frequency of somatic EGFR mutations varies from 30% to 50% among East Asians to approximately 10% among Caucasians [4]. Currently, EGFR-tyrosine kinase inhibitor (TKI) is the standard first-line treatment for patients with advanced, recurrent, or metastatic NSCLC harboring an EGFR mutation [5]. Preclinical data have demonstrated that gefitinib, icotinib and erlotinib can penetrate the blood-brain barrier (BBB) at concentrations adequate for initiating antitumor activity [6, 7]. The reported cerebrospinal fluid (CSF)/plasma concentrations of the first-line EGFR TKIs are approximately 0.6-2.5%[8-10]. Many retrospective and prospective studies have confirmed that EGFR TKIs have significant intracranial activity [9, 11]. A large phase 3, randomized controlled trial (BRAIN) reported by Wu et al. examined the efficacy of icotinib and whole-brain irradiation (WBI) in primary diagnosed NSCLC patients with EGFR mutations and at least three metastatic brain lesions [12]. The results showed icotinib has superior iPFS, PFS and ORR over WBI in EGFR-mutant advanced NSCLC with BM and has a well-tolerated safety profile. Therefore, the therapeutic status of EGFR TKIs in EGFR-mutant patients with BM has been confirmed. However, historically, brain metastases have been treated with surgical resection, stereotactic radiosurgery (SRS), or whole-brain radiotherapy (WBRT), either alone or in combination. Recently, a retrospective study reported in Journal of Clinical Oncology by Magnuson and his colleagues demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior overall survival (OS) in patients with EGFR-mutant NSCLC who develop brain metastases [5]. Therefore, despite the availability of various treatment options in this group of patients with BMs, including EGFR-TKIs, WBRT, and SRS, the optimal treatment combination or sequence has been unclear. BM is a complex and genetically heterogeneous population. Extensive efforts have focused on predicting outcomes for BM patients. The prognostic indexes have been widely applied in clinical practice, such as the Graded Prognostic Assessment (GPA) and the Disease-Specific GPA (DS-GPA). However, these indexes were mostly based on BM patients with unknown genetic status. Recently, an update of the DS-GPA using molecular markers (Lung-molGPA) was proposed by Paul W. Sperduto, incorporating gene alteration data into the DS-GPA. However, the prognostic value of the Lung-molGPA models for patients with EGFR mutation remains undetermined. The recent revolution in the treatment of patients with predictive biomarkers brought about the significant improvement of survival outcomes; thus, we sought to describe outcomes for patients with NSCLC and EGFR mutations and to identify prognostic factors for survival in a real-world population of EGFR-mutant NSCLC patients with BM that can be used to appropriately tailor treatment strategies. We also wanted to evaluate the therapeutic value and the prognostic effect of intracranial local therapy, chemotherapy and comprehensive treatments on patient survival. Meanwhile, we evaluate the prognostic value of the DS-GPA and Lung-molGPA indexes.
Patients and Populations
In this retrospective study, all patients aged 18 years or older with a diagnosis of NSCLC and with magnetic resonance imaging (MRI) confirmed BM diagnoses at our institution from January 2013 to December 2016 were identified. Other eligibility criteria included the following: harboring EGFR mutations and treatment with EGFR TKIs. Exclusion criteria included the following: KPS<50, diagnosed with BM during treatment with EGFR TKIs, and loss to follow-up. Baseline clinical characteristics were recorded by retrospective chart review, including age at diagnosis of BM, sex, smoking history, KPS, tumor histology, number of BM, ECM, whether the patient was symptomatic from BM and synchronous BM, type of EGFR mutation, intracranial local therapy delivered, and chemotherapy that was delivered. Patient follow-up by telephone was done until April 2018. Treatment response was evaluated, and survival data were collected and analyzed. This investigation was approved by the Zhejiang Center Hospital Ethics Committee.
MRI scans of the brain, along with positron emission tomography-computed tomography (CT) scans of the chest, were reviewed every 2 months. Tumor response to treatment was evaluated based on Response Evaluation Criteria in Solid Tumors version 1.1[13]. The primary outcome of this study was OS, defined as the duration between the diagnosis of BM and the time of death (all causes).
Patient OS was assessed using the Kaplan-Meier method. The log-rank test was used for comparison of survival curves of different characteristics. Prognostic factors for OS were analyzed by univariate and multivariate analyses. Variables with p<0.1 were added to the final multivariate Cox regression model. The hazard ratio (HR) and 95% confidence interval (CI) were calculated for all variables in the regression model. Statistical significance was set at p<0.05. All statistical analyses were performed using SPSS software, version 20.0 (SPSS Inc., Chicago, IL, USA).
From January 1, 2013, to December 31, 2016, a total of 746 patients were diagnosed with NSCLC with BM at Zhejiang Cancer Hospital. Of these patients, 269 EGFR-mutant patients had been treated with EGFR TKIs after the diagnosis of BM. After excluding those who met the exclusion criteria, 261 patients were enrolled in the study (Fig. 1). The median follow-up time for these patients was 32.7 months (95% CI 23.5-41.9). The median age was 54 years (range 30-79 years). The patients were predominantly younger than 65 years old (≤65 years old, 85.8%), female (59.4%), with a KPS score≥70 (71.6%), histology of adenocarcinoma (92.0%), lower number of BM (number of BM lesions≤3, 67%), without ECM (55.2%), without symptomatic BM (56.3%), with synchronous BM (72.4%), receiving local therapy (74.7%) and chemotherapy (56.3%). All patients were stratified according to the criteria of DS-GPA and Lung-molGPA. Overall, 42 patients (16.1%) had a DS-GPA score of 0-0.5, 102 patients (41.0%) were 1-1.5, 86 patients (33.0%) were 2-2.5, and 26 patients (10.0%) were more than 3. For the Lung-molGPA index [3], 7 patients (2.7%) were 0-1, 71 (27.2%) were 1.5-2, 125 (47.9%) were 2.5-3, and 58 (22.2%) were above 3.5. These EGFR-mutant cases included 138 (52.9%) exon 19 deletion, 90 (34.5%) L858R mutation, and 33 (12.6%) other EGFR mutations (including the presence of T790M mutation during treatment and other uncommon mutations). Due to medical insurance limitations, icotinib was not covered by Zhejiang Medicare until June 2016, whereas gefitinib and erlotinib were not covered until September 2017. Therefore, 38.8% patients received chemotherapy as first-line treatment in this study. Up to 69.3% patients had received icotinib in our study. Platinum doublet-chemotherapy was the most common chemotherapy regimen. The patient characteristics at baseline are detailed in Table 1.
Patient selection and exclusion criteria. Abbreviations: NSCLC, non-small cell lung cancer; BM, brain metastases; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; KPS, Karnofsky performance score.
Baseline characteristics
Age (30-79 years)
≤65 years old 224 (85.8%)
>65 years old 37 (14.2%)
Male 106 (40.6%)
Female 155 (59.4%)
Smoker 72 (27.6%)
Nonsmoker 189 (72.4%)
Performance status
KPS<70 74 (28.4%)
KPS≥70 187 (71.6%)
Histology n (%)
Adenocarcinoma 240 (92.0%)
Others 21 (8.0%)
Number of BM
≤3 175 (67.0%)
>3 86 (33.0%)
Yes 117 (44.8%)
No 144 (55.2%)
Symptomatic BM
With 147 (56.3%)
Without 114 (43.7%)
Synchronous BM
No 72 (27.6%)
EGFR mutation
Exon 19 deletion 138 (52.9%)
L858R 90 (34.5%)
Others 33 (12.6%)
Intracranial local therapy
DS-GPA score
0-0.5 42 (16.1%)
1-1.5 107 (41.0%)
≥3 26 (10.0%)
Lung-molGPA score
0-1 7 (2.7%)
1.5-2 71 (27.2%)
2.5-3 125 (47.9%)
≥3.5 58 (22.2%)
Abbreviations: BM, brain metastases; DS-GPA, diagnosis-specific graded prognostic assessment; ECM, extracranial metastases; EGFR, epidermal growth factor receptor; KPS, Karnofsky performance score; TKI, tyrosine kinase inhibitor.
Within the patients who received intracranial local therapy, 137 (70.2%) received WBRT, 37 (19.0%) received SRS or surgical resection, and 21 (10.8%) had a combination of the above. There were 161 (61.7%) patients who received EGFR TKIs as first line treatment. Among the 161 patients, 105 (65.2%) were treated with icotinib, 38 (23.6%) with gefitinib, and 18 (11.2%) with erlotinib. There was no difference in OS between different EGFR TKIs (p=0.087). Additionally, 117 (72.7%) of these 161 patients received radiotherapy (RT), 86 received upfront RT (with an interval between RT and TKI treatment ≤1 months), and 31 received deferral RT. We found no significant difference in OS between the two groups (p=0.395).
Postprogression Treatment
It should be noted that osimertinib did not enter the Chinese market until April 2017; hence, only 24 patients received osimertinib after the progression of first-line EGFR TKIs. We found that patients treated with osimertinib achieved a survival benefit from its use (p=0.011).
OS and Prognosis
The median OS was 23.0 months (95% CI 20.0-26.0, Fig. 2). By univariate analysis, significantly shorter OS was noted in patients older than 65 years (p=0.025), KPS <70 (p=0.003), and patients with ECM (p=0.00). Patients who received chemotherapy were more likely to have longer OS than those who did not (28.0 vs 16.5, p=0.01). Meanwhile, patients who received local therapies also had longer OS than those who did not receive local therapies (24.9 vs 16.0, p=0.00). In addition, we found patients who revived SRS or surgical resection tended to have longer OS than those who underwent other local therapy methods (SRS or surgical resection 34.4 vs WBRT 23.2 vs combination 19.0), though it didn't reach the statistical significance (p=0.067). There was also no difference in the patients respect to sex, smoking history, EGFR mutation type, number of BM. In multivariate analyses using multiple Cox proportional hazards models, we observed that performance status (KPS<70, p=0.010), extracranial metastases (ECM) at time of brain metastases (p=0.001), receiving intracranial local treatment (p=0.005) and chemotherapy (p=0.005) were independent prognostic factors for OS, while age was not (p=0.087). As for the prognostic index, survival by DS-GPA and Lung-molGPA group showed excellent separation between groups (p=0.000; p=0.000; Fig. 3) The survival times for all patients with DS-GPA scores of 0-0.5, 1.0-1.5, 2.0-2.5, and more than 3 were 16.0, 17.7, 27.0 and 42.0 months, respectively. In addition, survival times for patients with Lung-molGPA scores of 0-1.0, 1.5-2.0, 2.5-3.0, and more than 3.5 were 15.0, 16.0, 23.7 and 32.0 months, respectively. Taken together, both the DS-GPA and Lung-molGPA models predicted the prognosis of NSCLC patients with BM (P=0.000). However, the Lung-molGPA model did not show further superiority of its predictive effect. In multivariate analyses using multiple Cox proportional hazards models, we observed that performance status (KPS≥70; HR 0.639, 95% CI 0.455-0.897, p=0.010), ECM (HR 1.733, 95% CI 1.256-2.391, p=0.001), local therapy (HR 0.607, 95% CI 0.430-0.857, p=0.005) and chemotherapy (HR 0.629, 95% CI 0.455-0.870, p=0.005) were independent prognostic factors for OS, while age was not (HR 1.436, 95% CI 0.949-2.172, p=0.087; Table 2, Fig. 4).
Univariable and Multivariable Analyses of Covariables Associated With OS
Multivariate analysis-reduced
Hazard ratio
Age (>65 y/o) 1.579 1.052-2.369 .025 1.436 0.949-2.172 .087
Gender (male) 1.141 0.846-1.540 .384
Smoking history (smoker) 1.077 0.781-1.485 .649
KPS≥70 0.626 0.457-0.859 .003 0.639 0.455-0.897 .010
BM numbers >3 0.946 0.687-1.302 .729
ECM 1.744 1.287-2.362 .000 1.733 1.256-2.391 .001
EGFR mutation 1.024 0.840-1.247 .343
Intracranial local therapy 0.546 0.392-0.761 .000 0.607 0.430-0.857 .005
Chemotherapy 0.598 0.442-0.808 .001 0.629 0.455-0.870 .005
DS-GPA score 0.675 0.558-0.818 .000
Lung-molGPA score 0.667 0.551-0.807 .000
Abbreviations: BM, brain metastases; DS-GPA, diagnosis-specific graded prognostic assessment; ECM, extracranial metastases; EGFR, epidermal growth factor receptor; KPS, Karnofsky performance score; OS, overall survival.
Kaplan-Meier curve illustrating OS of EGFR-mutant NSCLC patients with brain metastases showed a median OS (months from start of brain metastasis) of 23.0 months (95% CI: 20.0-26.0).
Kaplan-Meier analysis comparing overall survival in patients based on the DS-GPA and Lung-molGPA indexes. (A): For the DS-GPA, patients with a score of more than 3 had the longest median OS, 42.0 months (95% CI: 16.0-68.8), followed by those with a score of 2-2.5 (median OS=27.0 months; 95% CI: 22.6-31.4), those with a score of 1-1.5 (median OS=17.7 months; 95% CI: 14.4-21.0), and those with a score of 0-0.5 (median OS=16.0 months; 95% CI: 8.6-23.4). (B): For the Lung-molGPA, patients with a score of more than 3.5 had the longest median OS, 32.0 months (95% CI: 21.4-42.6), followed by those with a score of 2.5-3 (median OS=23.7 months; 95% CI: 18.9-28.5), those with a score of 1.5-2 (median OS=16.0 months; 95% CI: 11.5-20.6), and those with a score of 0-1 (median OS=15.0 months; 95% CI: 2.2-27.8).
Kaplan-Meier analysis showing survival based on different factors for NSCLC: (A)age (mOS: 23.7 vs 18.8 months, p=0.025), (B)KPS (mOS: 16.0 vs 24.9 months, p=0.003), (C)ECM (mOS: 32.0 vs 19.7 months, p=0.000), (D)BM numbers (mOS: 22.7 vs 23.6 months, p=0.729), (E)intracranial local therapy (mOS: 16.0 vs 24.9 months, p=0.000), (F)chemotherapy (mOS: 16.5 vs 28.0 months, p=0.001)
In this study, we found that KPS, absence of ECM, receiving intracranial local therapy and the administration of chemotherapy were independent prognostic factors for OS in patients harboring an EGFR mutation and brain metastases, in real-world practice. While age, number of BM and EGFR mutation type showed no impact on survival. We also found that the sequence of RT and EGFR TKIs had no significant effect on prognosis. The DS-GPA and Lung-molGPA indexes were still valid in predicting the prognosis of EGFR-mutant patients with BM, but the Lung-molGPA index did not show further superiority in NSCLC patients with BM and clear gene status.
Extracranial metastases as a prognostic predictor have been reviewed previously. Regardless of the Recursive Partitioning Analysis (RPA) or the DS-GPA index or any other prognostic index, ECM has always been an independent prognosticator influencing survival and is most often the strongest one[14-17]. In our study, ECM was once again confirmed to be prognostic. It is reasonable to assume that patients with ECM would live shorter periods than those without ECM. The underlying mechanism could be that patients with ECM once had a heavy disease burden. Treatments for these patients should be both intracranial and extracranial, which might be the possible reason for their worse prognosis. As Kocher et al. pointed out, the presence of ECM may also influence survival by reseeding the brain parenchyma, thus forming another potential source of new brain metastasis, as indicated by the presence of multiple extracranial metastases[18]. Meanwhile, patients with good control of ECM-associated activities have a certain curative rate and can benefit more from local treatment.
The number of BM has been reported to be a poor prognostic factor in NSCLC. Our study, however, found that the number of BM was not associated with survival. This finding may imply that the number of BM is not a reliable prognostic factor in the setting of EGFR mutations and TKI therapy. Previous database analysis of the prognostic indexes included EGFR wild-type group, and this inclusion may have affected the accuracy of prognosis for EGFR-mutant patients[3, 15, 17].We assume that TKIs have a good control of intracranial lesions in patients with EGFR mutations and BM. Therefore, the number of BM may not influence the efficacy of TKIs.
In our analysis of different EGFR mutation subgroups, we found EGFR mutation type had no impact on OS. Median OS of patients with exon 19 deletion, L858R mutation and other EGFR mutations in our study was 23.6 months, 19.7 months and 27.0 months, respectively (p=0.343). Former studies have found exon 19 deletion achieved better OS than L858R mutation in NSCLC patients receiving EGFR-TKI treatments [4, 19, 20]. A similar result was also found in EGFR-mutant patients with BM [6]. Nevertheless, there were reports that indicated that the type of EGFR mutation was not predictive for the development of brain metastases or the survival of patients [21]. A number of studies have reported that the efficacies of EGFR-TKIs are distinct among different mutant subtypes. However, most patients with BM would be willing to undergo intensification therapy for intracranial lesions. This result could be the reason that, in our study, EGFR mutation type had no apparent impact on the survival of patients with BM.
A series of studies evaluating the use of cranial local therapies in patients with BM has been performed and suggests a survival benefit from local therapy. In our study, we noted that the administration of local therapy can significantly improve survival and was a prognostic predictor. In the current era of targeted therapy, EGFR TKIs alone have demonstrated activity against intracranial disease in EGFR-mutant NSCLC [11, 22, 23]. In addition, a systematic review and meta-analysis of 12 studies found that, relative to treatment with TKIs alone, cranial radiotherapy followed by EGFR TKIs improves intracranial control and survival outcomes in EGFR-mutant NSCLC with BM [24]. Multiple studies have shown patients with EGFR mutation to be highly radiosensitive in both the preclinical and clinical settings, thereby making the ablation of BM a distinct possibility [25, 26]. It was previously reported that local control rates of SRS in the treatment of EGFR-mutant brain metastases had reached 100% and 93% [25, 27]. Another multi-institutional analysis also revealed the impact of RT followed by EGFR TKIs on patient outcomes was most pronounced in patients with a more favorable prognosis (dsGPA,2-4)[5]. For patients with good DS-GPA scores, more active and reasonable intracranial local treatment is recommended.
In the subgroup of patients who received EGFR TKIs as first-line treatment, no significant difference in OS was noted between patients who received upfront RT and those who did not (p=0.395), which is a different result than reported in previous studies. A retrospective study found that the use of upfront EGFR-TKI, and deferral of RT, would result in inferior survival in patients with EGFR-mutant NSCLC who develop BM [28]. Extensive efforts have focused on the optimal sequence of RT for BM patients. Magnuson et al. also noted significantly worse survival in those who had delayed brain RT, regardless of whether it was SRS or WBRT [5, 29]. However, this finding needs to be interpreted with caution because the relatively small sample size and retrospective design may lead to selection bias for treatment. Prospective, multi-institution randomized trials are urgently needed to determine the optimal treatment combination or sequence. The BRAIN study indicated that, in patients with EGFR-mutant NSCLC and multiple brain metastases, icotinib was more recommended as a first-line therapeutic option over WBI treatment [12]. It is recommended that through the use of highly active targeted therapies, WBRT can be safely postponed in patients with EGFR mutation and BM [30]. However, the optimal sequences between EGFR TKI and RT are still controversial.
We also found that the administration of chemotherapy on the basis of EGFR TKIs can significantly improve the survival and was a prognostic predictor. Accordingly, chemotherapy could achieve better systemic disease control. In our study, 147 patients received chemotherapy, with 97 (66.0%) receiving pemetrexed-based chemotherapy. It is reported that some drugs might, to some extent, penetrate the blood-brain barrier (BBB) and gain intracranial control. Barlesi et al. previously demonstrated that pemetrexed-based chemotherapy had the greatest activity, as well as a favorable safety profile, in managing NSCLC patients with inoperable BM [31]. It should be noted that this study did not observe whether the adoption of chemotherapy on the basis of EGFR TKIs would bring more adverse effect.
The results of our study confirmed the DS-GPA index remains a robust tool and was useful for estimating survival in EGFR-mutant patients with BM. However, the Lung-molGPA index updated by Sperduto et al did not appear superior when compared to DS-GPA in the gene-specific NSCLC patients with BM in this study. Perhaps a more accurate and user-friendly tool could be developed for patients with specific oncogenic driver genes.
This study is limited by its retrospective nature. Because it is a single-institutional study, there may have been bias in choosing patients for enrollment. Therefore, the results reported here are not entirely representative of a large sample population. Another limitation of this study is that follow-up data on toxicities, cognitive impairment and quality of life were lacking; therefore, we were unable to analyze these factors.
In conclusion, this study provided real-world evidence for the survival and prognosis of EGFR-mutant NSCLC patents with BM. Performance status (KPS≥70), absence of ECM, the administration of local treatment or chemotherapy might all predict superior OS in EGFR-mutant NSCLC patients who develop brain metastases. While the DS-GPA and Lung-molGPA indexes were still robust tools, we propose a more accurate and user-friendly tool that applies to patients including specific gene status and BM. Further studies with large sample sizes are warranted.
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27. Wang TJ, Saad S, Qureshi YH, Jani A, Nanda T, Yaeh AM. et al. Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?. Neuro-oncology. 2015;17:1022-8
28. Magnuson WJ, Yeung JT, Guillod PD, Gettinger SN, Yu JB, Chiang VL. Impact of Deferring Radiation Therapy in Patients With Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Develop Brain Metastases. International journal of radiation oncology, biology, physics. 2016;95:673-9
29. Zhou L, Deng L, Lu Y. Epidermal Growth Factor Receptor Mutations in Non-Small-Cell Lung Cancer With Brain Metastasis: Can Up-Front Radiation Therapy Be Deferred or Withheld?. Journal of Clinical Oncology. 2017;35:1033-5
30. Martinez P, Mak RH, Oxnard GR. Targeted Therapy as an Alternative to Whole-Brain Radiotherapy in EGFR-Mutant or ALK-Positive Non-Small-Cell Lung Cancer With Brain Metastases. JAMA Oncol. 2017;3:1274-5
31. Barlesi F, Gervais R, Lena H, Hureaux J, Berard H, Paillotin D. et al. Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07-01). Annals of Oncology. 2011;22:2466-70
Corresponding author: Dr. Yun Fan, Department of Thoracic Medical Oncology; Key laboratory Diagnosis and Treatment Technology on Thoracic Oncology (esophagus, lung), Zhejiang Caner Hospital, No 1, East Banshan Road, Gongshu District, Hangzhou, 310022, Zhejiang, People's Republic of China. Fax +86 571 8812 2589. Email: fanyun_zjcccom


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Search for: [Authors = Piękoś, M]
Lead-Free Casting Brasses. Investigations of the Corrosion Resistance and Shaping of Microstructure and Properties
J. Kozana A. Garbacz-Klempka M. Piękoś
Keywords Innovative foundry technologies and materials Lead-free casting brasses Mechanical properties microstructure
The ecological factor is very important in shaping properties of alloys. It leads to a limitation or elimination, from the surroundings, of harmful elements from the heavy metals group. The so-called eco-brasses group comprises common lead-free brasses containing 10 to 40% of zinc and arsenic brasses of a high dezincification resistance. Among standardized alloys, CW511L alloy ( acc. to EN standard) or MS-60 alloy (acc. to DIN) can be mentioned. Investigations were performed on two different kinds of metal charges: ingots cast by gravity and the ones obtained in the semi-continuous casting technology with using crystallizers. The casting quality was analysed on the basis of the microstructure images and mechanical properties. The investigations also concerned increasing the corrosion resistance of lead-free alloys. This resistance was determined by the dezincification tendency of alloys after the introduction of alloying additions, i.e. aluminium, arsenic and tin. The investigations focused on the fact that not only alloying additions but also the production methods of charge materials are essential for the quality of produced castings. The introduced additions of aluminium and tin in amounts: 0÷1.2 wt% decreased the dezincification tendency, while arsenic, already in the amount of 0.033 wt%, significantly stopped corrosion, limiting the dezincification process of lead-free CuZn37 brass. At higher arsenic contents, corrosion occurs only within the thin surface layer of the casting (20 μ).
Structure Analysis and Properties of Unleaded Brasses
S. Rzadkosz A. Garbacz-Klempka J. Kozana M. Piękoś
Influence of Modification in Centrifugal Casting on Microstructure and Mechanical Properties of Silicon Bronzes
A. Garbacz-Klempka J. Kozana M. Piękoś M. Papaj P. Papaj M. Perek-Nowak
Keywords Innovative foundry technologies and materials Cu-Si Alloys Centrifugal casting microstructure mechanical properties
Silicon bronzes are characterised by good mechanical properties and by high corrosion and mechanical wear resistance. The process of sleeve casting by means of the centrifugal casting with the horizontal axis of the mould rotation was analysed. The assessment of the influence of modification and centrifugal casting parameters on the microstructure and mechanical properties of alloys was carried out in the hereby work. Zirconium was applied as a modifier. Speed of rotation of the mould was the variable parameter of the centrifugal casting. The investigation results were summarised on the basis of the microstructure analysis and mechanical properties determination: UTS, proof stress, A10 and BHN. The experiment aimed at finding the information in which way the modification together with changing the pouring parameters influence the mechanical properties of the CuSi3Zn3FeMn alloy.
Research on Technology of Alloyed Copper Casting
A. Garbacz-Klempka S. Rzadkosz J. Kozana M. Piękoś M. Kranc W. Cieślak
Keywords Casting technology Copper Alloyed copper Copper deoxidation heat treatment
The work presents experiment results from the area of copper casting technology and chosen examples of alloyed copper. At present, copper casting technology is applied in many branches of industrial manufacturing, especially in the sector of construction, communications, arms and power engineering. Alloyed copper, containing slight additions of different elements and having special physio-chemical properties, is used in a special range of applications. Copper technology and alloyed copper analyses have been presented, these materials being used for cast manufacturing for power engineering. The quality of casts has been assessed, based on their microstructure analysis, chemical content and the cast properties. During the research, special deoxidizing and modifying agents were applied for copper and chosen examples of alloyed copper; also exemplary samples were tested with the help of metallographic analysis, electrical conductivity and gaseous impurities research.
Structure and Properties Research of Casts Made with Copper Alloys Matrix
S. Rzadkosz J. Kozana M. Piękoś A. Garbacz-Klempka M. Kranc
Archaeometallurgical Investigations of the Early Iron Age Casting Workshop at Kamieniec. A Preliminary Study
M. Perek-Nowak J. Kozana M. Piękoś A. Garbacz-Klempka Ł. Kowalski J. Gackowski G. Szczepańska
Keywords Non-destructive testing Investment casting X-ray fluorescence spectroscopy Archaeometallurgy Lusatian culture
This preliminary study characterizes the bronze metalworking on a defensive settlement of the Lusatian culture in former Kamieniec (Chełmno land, Poland) as it is reflected through casting workshop recovered during recent excavations. Among ready products, the ones giving evidence of local metallurgy (e.g. casting moulds and main runners) were also identified. With the shrinkage cavities and dendritic microstructures revealed, the artifacts prove the implementing a casting method by the Lusatian culture metalworkers. The elemental composition indicates application of two main types of bronzes: Cu-Sn and Cu-Pb. Aside these main alloying additions, some natural impurities such as silver, arsenic, antimony and nickel were found which may be attributed to the origin of the ore and casting technology. The collection from Kamieniec was described in terms of its structure and composition. The investigations were made by means of the energy dispersive X-ray fluorescence spectroscopy (ED-XRF), scanning electron microscopy (SEM) coupled with an energy dispersive Xray analysis system (EDS) and optical microscopy (OM). In order to fingerprint either local or non-local profile of the alloys, the ED-XRF data-set was statistically evaluated using a factor analysis (FA).
Metallurgical Slags as Traces of a 15th century Copper Smelter
J. Kozana M. Piękoś A. Garbacz-Klempka Z. Kwak M. Wardas-Lasoń
Keywords Environment protection Archaeometallurgy Metallurgy of copper Environment pollution Copper Lead Silver
The research focuses on assessing the metal content, mainly copper, lead, iron and also silver in metallurgical slag samples from the area where historical metallurgical industry functioned. In the smelter located in Mogiła, near Krakow (southern Poland), whose operation is confirmed in sources from 1469, copper was probably refined as well as silver was separated from copper. Based on the change of chemical and soil phase content and also taking cartographic and historical data into account, considering the restrictions resulting from the modern land use the area was determined whose geochemical mapping can point to the location of the 15th century Jan Thurzo's smelter in Mogiła near Krakow. Moreover, using the same approach with the samples of this kind here as with hazardous waste, an attempt has been made to assess their impact on the environment. Thereby, taking the geoenvironmental conditions into account, potential impact of the industrial activity has been assessed, which probably left large scale changes in the substratum, manifested in the structure, chemical content and soil phase changes. Discovering areas which are contaminated above the standard value can help to identify historical human activities, and finding the context in artefacts allows to treat geochemical anomalies as a geochronological marker. For this purpose the best are bed sediments, at present buried in the ground, of historical ditches draining the area of the supposed smelter. Correlating their qualities with analogical research of archeologically identified slags and other waste material allows for reconstructing the anthropopressure stages and the evaluation of their effects. The operation of Jan Thurzo's smelter is significant for the history of mining and metallurgy of Poland and Central and Eastern Europe.
Analysis of a Castings Quality and Metalworking Technology. Treasure of the Bronze Age Axes
P. Długosz A. Garbacz-Klempka Z. Kwak Ł. Karczmarek J. Kozana M. Piękoś M. Perek-Nowak
Archives of Foundry Engineering | 2018 | vol.18 | No 3 | 179-185 | DOI: 10.24425/123622
Keywords non-destructive testing archeometallurgy Tin bronze X-ray spectroscopy Castings Defects
Cast axes are one of the most numerous categories of bronze products from earlier phases of the Bronze Age found in Poland. They had multiple applications since they were not only used objects such as tools or weapons but also played the prestigious and cult roles. Investigations of the selected axes from the bronze products treasure of the Bronze Age, found in the territory of Poland, are presented in the hereby paper. The holder of these findings is the State Archaeological Museum in Warsaw. Metallurgical investigations of axes with bushing were performed in respect of the casting technology and quality of obtained castings. Macroscopic observations allowed to document the remains of the gating system and to assess the range and kind of casting defects. Light microscopy revealed the microstructure character of these relicts. The chemical composition was determined by means of the X-ray fluorescence method with energy dispersion (ED-XRF) and by the scanning electron microscopy with X-ray energy dispersion analysis in micro-areas (SEM-EDS). The shape and dimensions of cores, reproducing inner parts of axes were identified on the basis of the X-ray tomography images. Studies reconstructed production technology of the mould with gating system, determined chemical composition of the applied alloys and casting structures as well as revealed the casting defects being the result of construction and usage of moulds and cores.
Assessment of Impact of Nickel Additions on Tin Bronzes
A. Garbacz-Klempka E. Czekaj M. Perek-Nowak J. Kozana M. Piękoś
Keywords Wear resistant alloys Tin bronze Microstructure Alloy additives Cu–Sn–Ni
High prices of tin and its limited resources, as well as several valuable properties characterising Cu-Sn alloys, cause searching for materials of similar or better properties at lower production costs. The influence of various nickel additions to CuSn10 casting bronze and to CuSn8 bronze of a decreased tin content was tested. Investigations comprised melting processes and casting of tin bronzes containing various nickel additions (up to 5%). The applied variable conditions of solidification and cooling of castings (metal and ceramic moulds) allowed to assess these alloys sensitivity in forming macro and microstructures. In order to determine the direction of changes in the analysed Cu-Sn-Ni alloys, the metallographic and strength tests were performed. In addition, the solidification character was analysed on the basis of the thermal analysis tests. The obtained results indicated the influence of nickel in the solidification and cooling ways of the analysed alloys (significantly increased temperatures of the solidification beginning along with increased nickel fractions in Cu-Sn alloys) as well as in the microstructure pattern (clearly visible grain size changes). The hardness and tensile strength values were also changed. It was found, that decreasing of the tin content in the analysed bronzes to which approximately 3% of nickel was added, was possible, while maintaining the same ultimate tensile strength (UTS) and hardness (HB) and improved plasticity (A5).

redpajama_set_name: RedPajamaCommonCrawl


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Pitchfork Music Festival 2019 Set Times Revealed
Photo by Kristina Pedersen / Graphic by Marina Kozak
Don't miss Robyn, Belle and Sebastian, HAIM, Sky Ferreira, Earl Sweatshirt, Parquet Courts, the Isley Brothers, and more
This year's Pitchfork Music Festival is just one month away! The fest runs from July 19 to 21 at Chicago's Union Park. Headlining on Friday, July 19 are HAIM, playing their only show of 2019. Then, on Saturday, the Isley Brothers will perform a 60th Birthday Celebration. Robyn closes out Pitchfork Fest on Sunday, July 21.
Other notable sets at Pitchfork Fest 2019 include Belle and Sebastian playing If You're Feeling Sinister and Stereolab's first North American show in over a decade. Check out all the set times below.
Tickets to Pitchfork Music Festival 2019 are on sale for $85 a day or $190 for a three-day pass. Get your Pitchfork Fest 2019 tickets here!
Pitchfork Music Festival 2019
(All times listed in Central Standard Time)
Friday, July 19:
1:00-1:40: Great Black Music Ensemble (Green)
1:45-2:25: MIKE (Red)
2:30-3:15: Standing on the Corner (Green)
2:45-3:30: Rico Nasty (Blue)
3:20-4:10: Valee (Red)
4:00-4:45: Grapetooth (Blue)
4:15-5:10: Sky Ferreira (Green)
5:15-6:10 Earl Sweatshirt (Red)
5:15-6:10: Julia Holter (Blue)
6:15-7:15: Pusha-T (Green)
6:30-7:15 Soccer Mommy (Blue)
7:25-8:25: Mavis Staples (Red)
7:45-8:30: Low (Blue)
8:30-9:50: HAIM (Green)
Saturday, July 20:
1:00-1:40: Lala Lala (Green)
1:45-2:25: Ric Wilson (Red)
2:30-3:15: CHAI (Green)
2:45-3:30: Tirzah (Blue)
3:20-4:10: Cate Le Bon (Red)
4:00-4:45: Jay Som (Blue)
4:15-5:10: Parquet Courts (Green)
5:15-6:10 Kurt Vile (Red)
5:15-6:10: Amber Mark (Blue)
6:15-7:15: Stereolab (Green)
6:30-7:15 Freddie Gibbs (Blue)
7:25-8:25: Belle and Sebastian (Red)
7:45-8:30: Jeremih (Blue)
8:30-9:50: The Isley Brothers (Green)
Sunday, July 21:
1:00-1:40: Dreezy (Green)
1:45-2:25: Flasher (Red)
2:30-3:15: black midi (Green)
2:45-3:30: Tasha (Blue)
3:20-4:10: JPEGMAFIA (Red)
4:00-4:45: Ibeyi (Blue)
4:15-5:10: Clairo (Green)
5:15-6:10 Khruangbin (Red)
5:15-6:10: Amen Dunes (Blue)
6:15-7:15: Whitney (Green)
6:30-7:15 Neneh Cherry (Blue)
7:25-8:25: Charli XCX (Red)
7:45-8:30: Snail Mail (Blue)
8:30-9:50: Robyn (Green)
TagsPitchfork2019Pitchfork Music FestivalFestivals
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Short Film: Guy Maddin's Sissy-Boy Slap-Party
By Mike Everleth ⋅ September 30, 2011
Raw, half-naked violence explodes across the screen in a gritty tableaux of sweaty brutality in Guy Maddin's short film Sissy-Boy Slap-Party, a film for which a title was never more accurate. Sailors in repose on an island paradise seemingly have no worries of war or danger — until a playful gesture is interpreted as an act of willful aggression. Soon, the innocent act of slight slapping becomes a relentless and unforgiving orgy of open-palmed face-smacking.
Sissy-Boy Slap-Party lends itself easily to comparison's to Jack Smith's legendary Flaming Creatures, from the loose plot structure to the washed-out exposures to the faux B-movie set and costuming to the homoerotic action. But, the film really takes a departure from its inspiration through Maddin's ecstatic and frantic editing when the slap party begins in earnest.
The film has a terrific rhythm to it as Maddin speeds up the editing to hyperkinetic speeds, but knows to periodically slow down on the cutting, allowing the audience to catch its breath before the action ramps back up again. Thus, the film has a very engaging rhythmic flow over its 6-minute runtime.
But what may be most interesting about the film is constructed is the way Maddin simulates sexual ecstasy through just editing when there is no sexual activity actually occurring between the men. In the last few minutes of the slapping, the film consists almost entirely of tight close-ups on the men's faces being battered back and forth. Elsewhere, a man banging on the drum is also in tight close up so that we can't see what his hands are doing. In fact, his hands could be doing anything off screen while his face contorts into spasms of pleasure and pain, obviously getting off on his own drumming and watching men slap each other senseless. It's sexual gratification through intimation of editing.
As of this writing, Sissy-Boy Slap-Party is one of several short films that Maddin has uploaded to Vimeo, where he at last joins many of his fellow Winnipeg filmmakers, such as Clint Enns, Jaimz Asmundson, Leslie Supnet and Heidi Phillips, who regularly promote and share their work on the video sharing site.
Guy Maddin | Watch Short Films
Flashback: 2nd Annual Chicago Underground Film Festival: Award Winners + Full Lineup


A small wind machine needs to carry insurance to protect the equipment, just like any other large investment you make. If a once in one hundred year storm destroys the machine, liability insurance is important to protect yourself, others and the interconnecting utility against unforeseen circumstances.
Some states, such as Minnesota, mandate that the machine have a certain amount of liability insurance, while in other states utilities set their own requirements for insurance.
Mick Sagrillo, a seasoned installer and wind energy advocate from Wisconsin put together a three-piece series on insuring small wind systems, which you can read by clicking here.


According to the tolerance values specified, the Sensitivity Analysis in OrCAD simulates circuit performance as those components parametric values change. It gives you an ordered list of critical components in your design. As a result, this allows you to save money by loosening the tolerance on those components which are not very critical for your goals and selecting cheaper ones.
Let's look at why a circuit designer would perform Sensitivity analysis on his/ her circuit design here.
Learn how Ericsson meets DDR and PCIE SPecs while avoiding crosstalk.


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More Than Just A Teacher
Aislinn Hunt, Writer
This semester Verrado welcomed many new teachers, one
Aislinn Hunt
Mr. Ward teaches his students about the legislative branch.
of them being Mr Mike Ward, the 2016/2017 school year.
Ward came to Verrado to teach Government and Economics after his high school government teacher "encouraged and empowered (him) to become an involved and educated individual."
Ward's teacher inspired him to become "a positive influence on (his) students."
After attending Buckeye Union High School, Mr. Ward attended Glendale Community College for two years to play baseball, one of his passions in life, and then transferred to Estrella Mountain Community College to finish his Associate's Degree, before earning his Bachelor's Degree in Education at ASU. Before coming to Verrado, Ward taught social studies at Desert Thunder Elementary School to seventh and eighth grade.
Students are taking a liking to Ward because of his exciting teaching style. "Mr Ward is a very
interesting human being and is sort of like one of the students. He has a very fascinating way of putting things and is very funny," said senior,Val Estrada.
Ward does not just inspire his pupils in the classroom, but also on the baseball field. Baseball has always been a huge part of his life, seeing as Ward has been playing since he was old enough to walk. Ward enjoys watching his players learn, grow, and become confident in their abilities, while enjoying the sport of baseball and its many life lessons within it.
As well as teaching an important part of our education at Verrado, Ward, and his wife, use and promote essential oils.
"My wife is a nurse and she believes highly in natural-holistic health practices. We both researched and heard about the essential oils and their ability to aid the human body naturally," said Ward.
In the past year he and his wife have both experienced and benefitted from the oils, which if you have ever wandered past Ward's room in the B wing, you will have noticed. "Plus, they work as great air fresheners too!"
Ward also exercises regularly with his wife, as they both do CrossFit.
"I enjoy CrossFit because it is never the same from day to day, and it pushes you to challenge yourself and push your limitations to become a better and stronger you! It is applicable to any/all individuals."
Using these oils, exercising with his wife, and coaching baseball are only pastimes because Ward says that, "My dream job is the one I have currently. I love teaching; I enjoy the fact that I can play a vital role in my students' lives."
Ward goes on to describe further.
"I love working at Verrado, the students and staff are all super accepting and open to everyone's own personality and who they are as individuals. The culture here is extremely fun, but yet focused on success and unity," said Ward.
Verrado high school
VHS News
One Response to "More Than Just A Teacher"
Q on November 29th, 2017 12:33 PM
Mr. Ward…Teacher of the year awarddddddd
School Clubs/Organizations
Isabella Chavez, Feature/A&E Editor • October 1, 2020
Verrado theater continues club this year and has already a late fall play lined up. I spoke to Abby Noel, club president, on all you need to know about the theater club this year! If you're wondering...
Christian Fellowship Club
Why Fashion Club Might Be For You
Verrado
William's Field
Sep 11 / Football
It's Important To Get A Flu Shot This Year
Good at video games? One university will give you a scholarship!
Buckeye Resident Inducted Into Arizona Veteran Hall Of Fame
Students Getting in the Spirit for Haunted Homecoming
Relieving Stress for Students
Elevate your future in a world of opportunities through FBLA!
Trump Administration Closes in on Banning E-Cigarettes
Reports of Car Accidents in VHS Parking Lot Leads to Cancelation of a Senior Tradition
Future Freshmen Prepare for their Future


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Home » News » Car News » BMW Unveils Next Generation X3
BMW Unveils Next Generation X3
By Rahul Kapoor | on June 27, 2017
The BMW X3 for the first time will get an M40i variant from BMW's 'M' division in the third generation model.
First introduced in 2003 and the second generation being introduced in 2010, BMW sold over 1.5 million units of the X3 which BMW refers to as a mid-size 'Sports Activity Vehicle'.
The third generation X3 is completely brand new as BMW has carefully designed the chassis and reduced unsprung mass allowing it to lose 55kgs from the outgoing generation. The new X3 also features new styling, making it look a part of BMW's family of latest generation models.
At the front, the X3 gets brand new LED headlamps with restyled fog lamps featuring LED technology. The kidney grille is now larger and features active air flap control. Right at the bottom-centre of the newly styled front bumper, the X3 also features a Driving Assistance Plus sensor which will allow BMW to include autonomous driving features. At the rear, the new X3 comes with an automatic tailgate, newly styled LED tail lamps, twin-tailpipes for all engine trims and a restyled rear bumper. BMW will also offer the new X3 with a front windscreen made of acoustic glass which will also be offered as options for the side windows. The new X3 will sit on lightweight alloy wheels ranging from 18-21 inch in size as options.
The 2018 BMW X3 also gets a brand new cabin with a completely redesigned interior and dashboard. The driver gets an optional 12.3 digital instrument cluster and full-colour heads-up display. A new leather-wrapped multifunction steering wheel, 10.2-inch touchscreen infotainment system with BMW iDrive and gesture control is also offered. Additional features include the options of an ambient air package, three-zone climate control and ambient lighting with light carpet are just a few from the extremely long options list. BMW has optimised the space inside the new model allowing it to have a total 550-litre boot space which is extendable up to 1,600-litres with the rear seats folded down.
The third-gen X3 will be offered in three trim options – xLine, Luxury Line and M Sport with a whole host of customisation features. The X3's engine line-up will feature three petrol and two diesel engines with various power outputs. These engines will produce 181bhp at least, with the most powerful engine churning out 355bhp. For the first time, the X3 will be offered with a variant from the 'M' division that will be available as the X3 M40i. All engines will come mated to an 8-speed Steptronic automatic transmission as standard.
The 2018 X3 will now also feature an option of the BMW Display Key. Additionally, it will feature a host of autonomous driving technology with the Active Cruise Control and the Driving Assistant Plus safety package. This includes Steering and lane control assistant, Lane Change Assistant and Lane Keeping Assistant with side collision protection.
Tags: BMW
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Here is your opportunity to get in on the ground floor of this to-be-built raised rancher located in the Felton country side! Construction has started but it is not too late to add your personal touches! The groundwork is complete for the septic and well and prepped to offer geothermal heat as a possibility for those interested in this energy efficient heating system. The home will be equipped with the Nest thermostat and will include smart outlets containing USB connectors throughout. Boasting 3 bedrooms and 2 full baths, the house offers an open concept living space, including a large great room, that provides plenty of space for you to stretch out with everything you need located on one floor. Situated on a 1 acre lot, this home will be ready by Summer 2019 in time to take advantage of the great views and abundant wildlife Southern York County has to offer from your front or rear deck. Call today to find out how to make it yours!


Been registered to the site for some time decided to finally make an official post, this is actually my second post. I have had my blackberry 8130 pearl since January. This site has been a gift when it comes to tips, tricks, and blackberry community happenings!
Now that you have your second post you're on your way to becoming a Crackberry Master! I love this site too.
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Keeping Music Alive in Our Schools
The Mr. Holland's Opus Foundation keeps music alive in our schools by donating musical instruments to under-funded music programs, and vital support services to school districts nationwide, giving economically-disadvantaged youth access to the many benefits of music education, leading them to success in school, and inspiring creativity and expression through playing music.
National relief fund for schools affected by natural disasters in the United States and U.S. Territories.
Connect with us and receive monthly updates
23 Years of Transforming Lives Through Music Education
The Foundation sees that students from low-income circumstances, whose parents can't afford to rent or buy instruments for them, are given an opportunity to play music in school. By offering school districts extra support and schools the instruments they need, all children will have access to music education and the joy of learning to play an instrument.
Donated Instruments
Students Impacted


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Александр Ильич Кварацхелия (13 мая 1909 года, село Накиани — неизвестно, Грузинская ССР) — советский хозяйственный, государственный и политический деятель, Герой Социалистического Труда.

Биография
Родился в 1909 году в селе Накиани на территории современного Чхороцкуского муниципалитета. С 1929 года — член ВЛКСМ, с 1932 года — член ВКП(б). С 1935 года обучался в Грузинской высшей сельскохозяйственной школе имени Сталина, которую окончил в 1937 года. В последующем служил политработником в Красной Армии. После армии — третий секретарь Зугдидского райкома партии, первый секретарь Цаленджихского райкома партии. В годы Великой Отечественной войны занимался снабжением продуктами фронта. За выдающееся руководство был награждён в 1944 году Орденом Трудового Красного Знамени.

В послевоенные годы избран первым секретарём Цхакаевского райкома партии. Занимался восстановлением довоенного сельскохозяйственного производства в районе. Благодаря его деятельности сельскохозяйственные предприятия в 1947 году перевыполнили в целом по району плановый сбор кукурузы на 47,3 %. Указом Президиума Верховного Совета СССР от 21 февраля 1948 года удостоен звания Героя Социалистического Труда за «получение высоких урожаев пшеницы и кукурузы в 1947 году» с вручением ордена Ленина и золотой медали «Серп и Молот» (№ 865).

Этим же Указом званием Героя Социалистического Труда были награждены административные, хозяйственные и партийные деятели Цхакаевского района председатель райисполкома Иосиф Берукович Гвадзабия, заведующий районным отделом сельского хозяйства Ной Ионович Гагуа, главный районный агроном Михаил Батломович Сабахтаришвили и директор Цхакаевской МТС Варлам Несторович Купрейшвили.

Избирался депутатом Верховного Совета Грузинской ССР 2-го и 3-го созывов.

С 1978 года — персональный пенсионер союзного значения. Дата смерти не установлена.

Награды и звания
 Герой Социалистического Труда (21.02.1948).
 орден Ленина (21.02.1948, 02.04.1966)
 орден Октябрьской Революции (08.04.1971)
 орден Отечественной войны I степени (24.02.1946)
 орден Трудового Красного Знамени (07.01.1944)
 орден «Знак Почёта» (12.12.1973)

Примечания

Ссылки

 Кварацхелия
 Кварацхелия Александр Ильич, Память народа

Первые секретари районных комитетов КП Грузии
Депутаты Верховного Совета Грузинской ССР 2-го созыва
Депутаты Верховного Совета Грузинской ССР 3-го созыва
Персональные пенсионеры союзного значения

redpajama_set_name: RedPajamaWikipedia


The touch screen totem, placed in the main square of Casciana Terme (Pisa) allows to visitors to easily browse through the useful informations of the territory, such as hotels, restaurants, news.
On the advertising totem is viewed a landing page made with Joomla. A custom Joomla template has been made to achieve a graphical interface with big sections, very easy to be browsed by people of all ages.
The custom Joomla template used for the touch screen totem has been made by Kiolezo component, one of our premium Joomla extensions.
Download this graphic as free Joomla template or as editable Kiolezo layout in Kiolezo Gallery section.
The touch screen advertising kiosk is made of a Full HD monitor with 1080x1920 pixel resolution, and it's totally waterproof, in way to resist to all kinds of bad weather.


Test passes if there is the word "PASS" below.
It should also allow there to be an unknown-character glyph.
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Light Image Resizer free image resizer and image converter.
Light Image Resizer is a free image resizer and free image converter resizes and simply converts images in batch mode with bulk editing. It is directly integrated into the windows shell context. Just right click and you can create copies or you can work on the original HQ pictures, then share your resized photos online.
Rename, sort or add a watermark to protect your pictures.
New – create custom pdf pages !


text:
Timberwolves, Evan Turner reportedly discussing buyout
By Kurt HelinFeb 8, 2020, 5:00 PM EST
Carmen Mandato/Getty Images
From the "a picture is worth a thousand words" file, if you want to understand just how much Minnesota overhauled its roster at the deadline, look at this photo from the introductory press conference.
That's a lot of new players pic.twitter.com/ZqnnIeYKeF
— Jon Krawczynski (@JonKrawczynski) February 7, 2020
Evan Turner is not in that photo because he sees the writing on the wall. Turner was traded from Atlanta to Minnesota as part of a massive four-team deal that brought the Hawks Clint Capela, and now he and the Timberwolves are talking buyout, according to Jon Krawczynski of The Athletic.
Evan Turner did not attend Wolves press conference today. Both sides discussing a buyout. Wolves are going young. The vet Turner would like to play for a contender, so the options are being explored.
Turner makes $18.6 million this year in the final year of his "summer of '16" contract Portland offered him, Minnesota likely would welcome the financial savings.
I've got Timberwolves $1,136,270 over the luxury-tax line. Hard to believe they'll pay tax for this team.
Evan Turner could surrender $922,099 in a buyout, sign rest-of-season minimum contract elsewhere and break even.
For Allen Crabbe, it's $802,269. But would team sign him?
— Dan Feldman (@DanFeldmanNBA) February 6, 2020
Boston, one of Turner's former teams, reportedly has some interest in a reunion. A number of playoff-bound teams should have interest in a solid veteran wing who can eat up minutes down the stretch of the season, allowing their starters/stars to get some rest. Turner will get picked up, but don't expect much of a playoff role.


text:
Tour the Art Park with artistic director
Doomsday clock remains at 100 seconds to midnight for second year
MNA Staff
THOMPSONVILLE — Michigan Legacy Art Park is offering a special guided tour with Artistic Director, Kaz McCue, on Sept. 16.
In addition to his staff role, McCue is a contributing artist to the park's permanent collection. His unique perspective as both curator and artist will provide special insight into the artwork.
This tour is free with park admission. Tours take approximately 1.5 hours along nearly two miles of rustic and hilly trails.
Meet at the Art Park trailhead by 10 a.m.
Michigan Legacy Art Park is a 501(c)(3) nonprofit located on a 30-acre preserve leased by Crystal Mountain. Michigan Legacy Art Park features 50 outdoor sculptures that celebrate Michigan's culture and history along nearly two miles of wooded hiking trails.
For more information on these and other events happening at Michigan Legacy Art Park this summer, visit michlegacyartpark.org or call (231) 378-4963
Local News Photos: Ice lines pier at 5th Avenue Beach


text:
Makrónissos  (, « l'île longue »), ou en français Macronèse, est une petite île de l'archipel des Cyclades, située non loin des côtes de l'Attique, à l'ouest de Kéa et au sud de la ville de Laurion. Elle dépend administrativement du district régional de Kéa-Kythnos.

Géographie
L'îlot a une superficie de  et un littoral de . Tout en longueur, il fait environ  de long sur 500 à  de large. C'est une île aride, rocheuse, au relief peu élevé. Son sommet est à .

Histoire

Antiquité
Dans l'Antiquité, l'îlot se serait appelé Hélène, car la belle, enlevée par Pâris, s'y serait arrêtée, soit en allant, soit en revenant de Troie. Des preuves archéologiques montrent que l'îlot était habité dès la fin du Néolithique (V millénaire ). On y a retrouvé notamment des morceaux de colonnes et les fondations d'un grand bâtiment antique.

Guerre des Balkans (1912-1913)
Pendant la guerre des Balkans, un grand nombre de prisonniers turcs ont été transférés à Makronissos et y ont vécu jusqu'à la signature de la paix avant d'être envoyés vers la Turquie. Nombre d'entre eux y sont cependant morts de maladies contagieuses et enterrés sur place.

Première Guerre mondiale (1914-1918)
C'est dans le chenal séparant Makronissos et l'île de Kéa que le navire-hôpital Britannic, jumeau du Titanic a coulé, le 21 novembre 1916, touché par une mine à 8h02 du matin. Il a touché le fond de la mer Égée 55 minutes plus tard. Il repose par  de fond. Le naufrage a fait une trentaine de morts. Plus de  ont été sauvées par les pêcheurs de Korissia, village de Kéa. Le navire ne transportait pas de blessés à ce moment-là ; il se rendait au front des Dardanelles.

Années 1920
L'île est utilisée comme camp de transit pour les réfugiés d'Asie Mineure, après la guerre gréco-turque (1919-1922).

Guerre civile (1946-1949)

Durant la guerre civile grecque et la dictature des colonels, Makronissos fut utilisé comme lieu de déportation des opposants politiques, principalement les communistes. L'îlot est ainsi considéré comme un monument commémoratif de la guerre civile.

En 1946, alors que le reste de l'Europe célébrait la paix retrouvée et pansait ses plaies, la Grèce entrait dans une période de misère et dans la guerre civile. Le Parti communiste de Grèce (KKE) était interdit, de même que l'Armée populaire de libération nationale (ELAS), qui avait mené la résistance contre l'occupant nazi, ainsi que le Front de libération nationale (EAM) et l'organisation politique de la jeunesse grecque (EPON). Des milliers de communistes et de militants de gauche ont été exécutés par des tribunaux militaires. Et près de  ont été exilés vers des îles reculées.

En 1946, à Makronissos, s'est ouvert le premier camp de concentration européen après la fin de la Seconde Guerre mondiale, 22 mois après la libération du dernier camp nazi à Dachau en avril 1945. Le camp a été rapidement soutenu par des fonds du plan Marshall, à la suite de la doctrine Truman. Concrètement, le premier camp de Makronissos a été mis sur pied par les troupes britanniques, qui y ont emprisonné le  de l'ELAS. Puis le  a été transféré de Thessalonique vers Makronissos ainsi que le , venu lui de l'île de Gioura. Les officiers de l'ELAS ont été transférés des îles où ils avaient été exilés vers Makronissos. Fin 1947, plus de  prisonniers avaient été transférés dans l'île.

1949-1967

En 1949, les citoyens exilés dans toutes les îles ont été déplacés vers Makronissos, sous la supervision de la gendarmerie. En octobre 1949, le parlement grec votait une loi sur la « rééducation nationale » et créait l'Organisation des camps de réhabilitation de Makronissos. Cette institution comprenait cinq ministres (Justice, Ordre public, Intérieur, Défense nationale et Éducation). Le but était de « réhabiliter » ces « mauvais » Grecs en citoyens modèles, considérés comme des « traîtres » et des « ennemis de l'État », bien qu'ils aient participé activement à la résistance nationale contre l'occupation nazie. Cette réhabilitation était appelée le « baptême de Siloam ». Les prisonniers vivaient sous des tentes sous l'extrême chaleur ou le froid, subissant la faim et surtout la soif, l'isolement, les menaces et le lavage de cerveau. Ils subissaient de multiples tortures, qui consistaient notamment à leur briser les os avec des barres de fer ou des baguettes de bambou. Certains sont devenus invalides, aveugles ou en sont morts. Ceux qui étaient brisés psychologiquement signaient une déclaration dans laquelle ils reconnaissaient leurs erreurs et sollicitaient le pardon. Ils étaient alors envoyés en première ligne pour lutter contre leurs camarades. Ceux qui refusaient de signer risquaient de passer devant une Cour militaire, et d'être exécutés par un peloton d'exécution devant la prison militaire de Makronissos.
En 1949, des milliers de militants de gauche avaient été arrêtés préventivement et déportés à Makronissos. En janvier 1949, des femmes ont aussi été emmenées dans le camp du .
Ce programme de « réhabilitation » a cessé mais des prisonniers politiques ont continué à être transférés à Makronissos jusqu'en 1957 dans les camps et jusqu'en 1960 dans la prison militaire. Selon les estimations, de  à  de toutes les régions de Grèce sont passées par Makronissos entre 1947 et 1958.

L'île a été définitivement abandonnée en 1961.

Aujourd'hui
Abandonnée, l'île de Makronissos est cependant restée propriété du ministère grec de la Défense jusqu'en 1974. En 1988, a été fondée l'Association panhellénique des combattants emprisonnés à Makronissos (PEKAM). Le 16 mai 1989, la ministre de la Culture Mélina Mercouri a proclamé Makronissos comme site historique et les bâtiments des camps conservés à ce titre. En 1995, un décret de protection de l'île était adopté.

Quelques déportés célèbres

 Yannis Ritsos (1909-1990), poète, a écrit une série de poèmes à Makronissos. Ils sont regroupés dans un ouvrage intitulé Temps pierreux, Makronissiotiques. « Ces poèmes ont été écrits à Makronissos, d'août à septembre 1949, au camp D de déportés politiques, avant que nous soyons transférés au bataillon B ; avant même de vivre toute l'horreur de Makronissos. Ces poèmes sont restés enterrés sur place dans des bouteilles scellées, et déterrés en juillet 1950 » (Yannis Ritsos, rabat du livre).
 Mikis Theodorakis, compositeur, a été détenu à Makronissos durant une année, de 1948 à 1949. Il y a enduré de terribles tortures. En mars, ses tortionnaires lui brisent la jambe droite, plusieurs côtes et lui endommagent un poumon. En août 2003, Mikis Theodorakis a donné deux concerts émouvants à Makronissos, où il est revenu après 45 ans.
 Manos Katrakis (1908-1984), acteur de théâtre.
Basile Krivochéine (1900-1985), moine du Mont Athos, puis archevêque orthodoxe russe.
 Aris Alexandrou (1922-1978), écrivain communiste
 Thanasis Vengos (1927-2011), acteur.
 Níkos Koúndouros (1926-), cinéaste.
 Stelios Kazantzidis (1932-2001), chanteur populaire, acteur de cinéma.
 Grigoris Bithikotsis (1922-2005), chanteur et compositeur populaire, interprète de nombreuses chansons composées par Mikis Theodorakis.
 Apóstolos Sántas (1922 -2011) « premier » résistant grec
 Titos Patrikios (1928-), sociologue, poète

Hommages cinématographiques
 Le Nouveau Parthénon (1975) de Kostas Chronopoulos et Giorgos Chryssovitsianos retrace la vie des prisonniers politiques dans les camps des îles de Gyaros et de Makronissos.
 Happy Day (1976) de Pantelís Voúlgaris est consacré au même thème.
 Makronissos (2008), de Ilias Giannakakis et Evi Karabatsou est un documentaire réalisé au terme de 10 années de recherche. Il présente des documents et films de l'époque ainsi que des témoignages particulièrement émouvants de rescapés du camp de concentration, mais aussi, pour la première fois, celui de l'ancien commandant du camp.
 Comme des lions de pierre à l'entrée de la nuit (2012), de Olivier Zuchuat

Notes et références

Voir aussi

Liens externes

Île en Égée-Méridionale
Île inhabitée en Grèce
Kéa (île)


When it comes to water damage and mold that which you have no idea can actually harm you! Water damage can result in increased insurance rates, decreased resell worth of house and property, and even health problems for many years if not correctly 24/7 plumber – as well as promptly – fixed water damage restoration.
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We are pleased to announce that the Toyota Landcruiser 200 series Gross Vehicle Mass (GVM) upgrade to 4000kg & Gross Combined Mass 7500kg is now available.
The Lovells 4000kg GVM Upgrade has have been granted Federal Compliance Approval as a Second Stage Manufacturer for the GVM (Gross Vehicle Mass) Upgrade of the TOYOTA LANDCRUISER LC200 WAGON.
For many years we have been upgrading the LC200 to 3800kg GVM in Australia. Now the 4000kg GVM upgrade kit has arrived. The Lovells PLATINUM SERIES 4000kg GVM Upgrade kit comes with an option of four (4) designs of coil springs for greater load/ride quality flexibility and our World famous 46mm bore Mono-Tube shock absorbers.
Note that the new RVD for this vehicle Approval was released prior to the revised DIRDC 0-4-6 Circular rulings, therefore the GCM can be revised beyond OE capacity for Federal Compliance Upgrades to 7500kg. If you have a Lovells 4000kg GVM upgrade fitted you are not eligible to increase your Braked Towing Capacity (BTC) to 4000kg. The maximum Towing Capacity is 3500kg if you have a 4000kg GVM upgrade fitted.


text:
AK: Tlingit carver featured in small-town, large-scale Smithsonian project
Tlingit master carver Wayne Price has a relationship with the ocean and the tides that runs deeper than most.
He carves dugout canoes in Haines and his work and words are set to hit the road in the spring as part of the Smithsonian's Water/Ways exhibit.
It's a traveling show from the Smithsonian Institution's Museum on Main Street designed for rural museums.
(Photo by Jillian Rogers, KHNS – Haines)
Wayne Price is standing in his home studio, explaining the maze of lines on his wood floor. He uses the lines to measure the canoe he's working on. His dugout canoes are big – about 30 feet long – and heavy.
The visitor is Smithsonian curatorial assistant Tiffany Cheng. Cheng found Price while looking for an Alaskan for the Water/Ways project through the Sealaska Heritage Institute. Price says he was happy to get involved mostly as a chance to help revive his art form, which he says is dying.
"The dugout canoes have been a big part of that all through 10,000 years of history," Price said. "We're in a desperate time right trying to keep that art alive."
Once Cheng arrived in Haines, She hopped on a local fishing boat with her cameraman to get some shots of Price and his crew paddling one of his prized canoes.
Cheng says Price was an obvious choice for the project.
"I wanted to meet him and talk to him about the craft of dugout canoes and the tradition and connection, the cultural connection to the water here in Alaska," Cheng said.
Besides Price and his canoes, the project includes a crabber in Louisiana, a shrimp boat captain in Mississippi and a conservationist who works in the Florida Everglades.
The project is a window into people's lives and a reflection of what water means to them.
"And the goal is not for us to tell the story it's for them to say it for themselves so that's our goal for coming out and meeting people like Wayne and hearing from them directly instead of just text on a wall or out of book," she said.
On her last day in Haines, Cheng was treated to a private singing and drumming performance by Price, Ted Hart and Zachary James.
For Price, sharing his passion comes easily. He enjoys teaching young people in the region how to carve and the significance of dugout canoes. And, he says, taking part in the Water/Ways project is another good way to spread the word about what he refers to as an endangered art. He says the canoes are one more way to foster traditional values.
"The Tlingit people come from the water. We're people of the tide. We've always said when the tide goes out it's time to go to eat. We gather all our food from the beach or the woods inside the beach," Price said. "Our whole way of living has been on the water and with the tides."
Price says the fact that interest in this specialized craft is waning, is simply a sign of the times. But local young people are getting more involved these days, he says, and taking an interest in learning the trade.
The Water/Ways exhibition will launch in May, 2016, in Florida, Idaho and Illinois first. The project will travel to various small towns across the U.S. for six years.
Previous articleThe current and future authority of Alaska's tribal governments
Next article49 Voices: Martin Lee Woods of Kotzebue


Marine salvage is the process of rescuing a ship, its cargo, or other property from peril. Salvage encompasses rescue towing, putting out fires, patching or repairing a ship, refloating a sunken or grounded vessel, moving a disabled vessel in order to clear navigation channels, and raising sunken ships or their cargo. Equipment involved in salvage operations may include cranes, floating dry docks, and support vessels (such as tugboats). Commercial divers may be called upon to perform underwater tasks and monitor progress below the surface.
Protecting the marine environment from pollution from cargoes such as oil or other contaminants is often an important part of salvage activities. Usually the vessel or valuable parts of the vessel or its cargo may be recovered for its resale value, or for scrap. The vast majority of salvage operations are contracted to qualified seamen and engineers working as professional salvors. Usually, contracted agents expect no financial reward unless the salvage operation is at least partially successful.
If salvage is not performed under a contract, then the rescuer must act voluntarily and aside from any legal duty to act, other than the acknowledged duty to render assistance to those in peril at sea or to attend after a collision. If the owner or the owner's agent is still on the ship, they can refuse offers of assistance. A vessel found entirely deserted or abandoned without hope or intention of recovery is considered derelict and is fair game for anyone who comes across it. It is not true, however, that the rescuer or salvor automatically becomes the owner of the property. The owner always has the option to reclaim his property by paying an appropriate reward.
Electronic devices classed for use in the marine environment. All electronics used onboard must be designed to fit in the small confines of a bridge and can come in contact with salt water, so they are made to be very water resistant or waterproof.
Sonar is a technique that uses sound to navigate, communicate with or detect other vessels, and to observe the distance and velocity of underwater objects. The acoustic frequencies used vary from extremely low (infrasonic) to very high (ultrasonic).


text:
Industry Sectors | Medical/Pharmaceutical
Medical Design & Manufacturing Breakthroughs
Once the stuff of science fiction, today's technologically advanced products can increase both the length and quality of our lives.
April/May 06
Medical design and manufacturing, one of the nation's fastest-growing industries, is targeting new advances to fight many of our most costly and harmful diseases. Reflecting its rapid growth, the medical technology industry, currently an $80 billion market, is projected to reach $140 billion by 2010, according to the Advanced Medical Technology Association (AdvaMed). The industry's products include pacemakers, defibrillators, orthopedic implants, diagnostic imaging equipment (such as ultrasound computer tomography), and magnetic resonance imaging (MRI) machines, as well as diagnostic tests that detect disease.
Mark Brager, AdvaMed's director of communications, says one of the major trends in medical design and technology is miniaturization, which allows implants to be smaller and produces less hospital time for faster recovery. He also cites mapping of the human genome (DNA). "It's an important scientific milestone that will lead to incredible breakthroughs in medical diagnostic technology," he says. In addition, advances in materials sciences are increasing the durability of implants. According to Brager, implants that used to last 10 years are now lasting 15 to 20 years and in the future will last 40 to 50 years. "It's important because people are living longer," he says. He also cites health information as one of the more important areas of technology, enabling providers to get rid of paper records, generate fewer medical errors, and increase efficiency.
In terms of site selection, Brager and others say medical design and manufacturing companies tend to group together in clusters of concentration, to avail themselves of reciprocal services, technical support, and professional resources. Brager lists the "Big Three" areas as Boston, the Twin Cities (called "medical alley"), and Southern California. Smaller versions of the Big Three are coming in Warsaw, Ind., Philadelphia, and areas of New Jersey.
It's no secret that today's medical manufacturing environment is a fast track, with the rapid emergence of new developments that can change market trends virtually overnight. Innovative products usher in new trends while older technology fades away. With that in mind, Medical Design Technology magazine, in its January 28, 2006 issue, pinpoints five different medical manufacturing sectors in the forefront of new trends: combination products, electronic miniaturization, nanotechnology, medical plastics, and lean manufacturing.
A combination products is one that combines more than one element, such as a medical device coated with a drug. The combination nature enables the product to perform its function more effectively, according to Barry Sall, senior consultant at PAREXEL International, providers of expertise in biopharmaceutical and medical device development to manufacturers worldwide. There's a wide variety of combination products, most being prescription products used by physicians. One that has enjoyed particular success is the drug-coated stent - a tube one-eighth of an inch in diameter and coated with a medication, which can be threaded into a blocked artery. The stent clears up the blockage and the drug prevents it from coming back by killing the cells that were creating it.
There's a trend toward increasing use of combination products because they provide greater insight into how medical devices react with the body. "As researchers gain additional understanding of these reactions, they can use drugs or biologies to enhance that interaction or reduce the possibility of an adverse reaction," says Sall. In general, combination products are more complex than traditional medical devices, he says, "so more complex manufacturing techniques are required to produce them. They require a lot of technical decisions which may involve process engineers or chemical engineers in some cases."
Sall says the industry involves many small entrepreneurial companies that want to be close to sources of venture capital, as well as intellectual resources in the form of schools and teaching hospitals. "Getting the right people together with the right knowledge is the main thing," he says.
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Ecolab Expands Huntington, Indiana, Operations Complex
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Aspen Laser Systems Relocates Headquarters to Lindon, Utah
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Hidden talents were revealed at the English department and Falvey Memorial Library's sixth annual Open Mic Poetry Reading. Lisa Sewell, Ph.D., an associate professor of English, served as this year's master of ceremonies and welcomed students, faculty, staff and special guests to the event, held on Wednesday, April 27, in the library first floor lounge.
Kevin Speirs, 2011 Senior Class Poet Honorable Mention, contributed "Homes," which has appeared on a poster displayed on Falvey's first floor. Seniors seeking to become Senior Class Poet have one of their poems made into a poster. To celebrate National Poetry Month, fourteen Senior Class Poet contestants had their poems on display in the Library during April.
Brittany Walker stepped up to the microphone next and offered "What's Love Got to Do with It?" Mike Mo shared "Another Drive." And Alexandra Edwards read "Because a Girl Is Not a Tree," which has been published in Arthology.
Special thanks go to Regina McFadden and the staff of the Library's Programming & Outreach team for providing the chairs, tables for refreshments and for Arthology, and the microphone.