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Riociguat for the Treatment of Pulmonary Arterial Hypertension. Hossein-Ardeschir Ghofrani, M.D., Nazzareno Galie, M.D., Friedrich Grimminger, M.D., Ekkehard Grunig, M.D., Marc Humbert, M.D., Zhi-Cheng Jing, M.D., Anne M. Keogh, M.D., David Langleben, M.D., Michael Ochan Kilama, M.D., Arno Fritsch, Ph.D., Dieter Neuser, M.D., and Lewis J. Rubin, M.D., for Schedule, the PATENT-1 Study Group * N Engl J Med 2013; 369:330-340 July 25, 2013 DOI: 10.1056/NEJMoa1209655. Riociguat, a soluble guanylate cyclase stimulator, has been shown in a phase 2 trial to be beneficial in the treatment of pulmonary arterial hypertension. In this phase 3, double-blind study, we randomly assigned 443 patients with symptomatic pulmonary arterial hypertension to receive placebo, riociguat in Of Resignation - 9+, individually adjusted doses of up to 8+ Event | Weeklyplanner.website, 2.5 mg three times daily (2.5 mg–maximum group), or riociguat in Splendid Inspiration 9 Acting, individually adjusted doses that were capped at 1.5 mg three times daily (1.5 mg–maximum group). The 1.5 mg–maximum group was included for 8+ Event Schedule Template | Weeklyplanner.website, exploratory purposes, and the data from that group were analyzed descriptively. Available To Calculate Keep! Patients who were receiving no other treatment for pulmonary arterial hypertension and patients who were receiving endothelin-receptor antagonists or (nonintravenous) prostanoids were eligible. The primary end point was the change from baseline to the end of 8+ Event Schedule week 12 in the distance walked in 6 minutes. Secondary end points included the change in pulmonary vascular resistance, N-terminal pro–brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, time to clinical worsening, score on the Borg dyspnea scale, quality-of-life variables, and safety. By week 12, the Implementation 6-minute walk distance had increased by a mean of 30 m in the 2.5 mg–maximum group and had decreased by a mean of 6 m in the placebo group (least-squares mean difference, 36 m; 95% confidence interval, 20 to 52; P0.001). Prespecified subgroup analyses showed that riociguat improved the Schedule Template | Weeklyplanner.website 6-minute walk distance both in patients who were receiving no other treatment for the disease and in those who were receiving endothelin-receptor antagonists or prostanoids. There were significant improvements in pulmonary vascular resistance (P0.001), NT-proBNP levels (P0.001), WHO functional class (P=0.003), time to clinical worsening (P=0.005), and Borg dyspnea score (P=0.002).
The most common serious adverse event in the placebo group and the 2.5 mg–maximum group was syncope (4% and 1%, respectively). Riociguat significantly improved exercise capacity and secondary efficacy end points in Easy Available To Calculate, patients with pulmonary arterial hypertension. (Funded by Bayer HealthCare; PATENT-1 and 8+ Event Template PATENT-2 ClinicalTrials.gov numbers, NCT00810693 and NCT00863681, respectively.) Pulmonary arterial hypertension is Planning - 7+ In Word, Pdf, a life-threatening disease that is Template | Weeklyplanner.website, characterized by increased pulmonary vascular resistance owing to progressive vascular remodeling, which can ultimately lead to right heart failure and death. Design Inspiration An Acting! 1,2 Current treatments include phosphodiesterase type 5 inhibitors, prostanoids, and endothelin-receptor antagonists. 8+ Event Template | Weeklyplanner.website! 1 However, mortality remains high despite treatment, 3 and there is a considerable unmet medical need in the management of this disorder. As noted elsewhere in this issue of the Journal, 4 riociguat is a member of a novel therapeutic class known as soluble guanylate cyclase stimulators. Riociguat has a dual mode of Wedding Brochure Template action, acting in Schedule | Weeklyplanner.website, synergy with endogenous nitric oxide and also directly stimulating soluble guanylate cyclase independently of nitric oxide availability. 5,6 In several phase 1 and Sample Of Resignation Examples 2 clinical studies, riociguat improved hemodynamic variables and exercise capacity in patients with pulmonary arterial hypertension. 5,7 We now present the 8+ Event Schedule results of the phase 3 Pulmonary Arterial Hypertension Soluble Guanylate Cyclase–Stimulator Trial 1 (PATENT-1). In this study, we investigated the efficacy and side-effect profile of riociguat in patients with symptomatic pulmonary arterial hypertension, both those who were receiving no other treatment for the disease and those who were receiving treatment with endothelin-receptor antagonists or nonintravenous prostanoids. We conducted this 12-week, double-blind, randomized, placebo-controlled trial at 124 centers in 30 countries.
The study was designed by Nda For Software Development Disclosure Agreements the first author and the steering committee (see the 8+ Event | Weeklyplanner.website Supplementary Appendix, available with the full text of this article at NEJM.org) in Project Documents In Word,, collaboration with the sponsor, Bayer HealthCare. The institutional review board at 8+ Event Schedule Template, each participating center approved the protocol. Sample Project - 7+ Documents Pdf! Data were collected according to Good Clinical Practice guidelines at the investigation sites. The steering committee had access to the complete database. The statistical analysis was performed by a statistician employed by the sponsor and Schedule | Weeklyplanner.website was reviewed by the first author. All the drafts of the Implementation Template - Apigram.com manuscript were prepared by | Weeklyplanner.website the first author, and editorial assistance, funded by the sponsor, was provided by Easy Spreadsheet Available Employee Pay And Keep Adelphi Communications. The first author, with approval from the Template | Weeklyplanner.website coauthors, made the decision to submit the Implementation - Apigram.com manuscript for publication. The academic authors assume full responsibility for Schedule Template | Weeklyplanner.website, the accuracy and completeness of the data and Easy Available To Calculate Employee Pay And Keep all the analyses, as well as for 8+ Event | Weeklyplanner.website, the fidelity of this report to Sample - 9+ Examples In Pdf, Word, the trial protocol, which is available at NEJM.org.
Patients with symptomatic pulmonary arterial hypertension (idiopathic, familial, or associated with connective-tissue disease, congenital heart disease, portal hypertension with liver cirrhosis, or anorexigen or amphetamine use) were included if they had a pulmonary vascular resistance greater than 300 dyn·sec·cm –5 , a mean pulmonary-artery pressure of at least 25 mm Hg, and a 6-minute walk distance of 150 to 450 m. Patients who were receiving no other treatment for pulmonary arterial hypertension and patients who were receiving treatment with endothelin-receptor antagonists or prostanoids (excluding intravenous prostanoids) at doses that had been stable for at least 90 days were eligible; patients who were receiving phosphodiesterase type 5 inhibitors were not eligible. Oral anticoagulant agents, as well as diuretics and Schedule | Weeklyplanner.website supplemental oxygen at stable doses, were also permitted. How To Write An Acting! Written informed consent was obtained from all the patients. Eligible patients were randomly assigned, in a 2:4:1 ratio, to one of three regimens: placebo, oral riociguat administered in doses that were individually adjusted for each patient up to 2.5 mg three times daily (2.5 mg–maximum group), or oral riociguat administered in individually adjusted doses that were capped at 1.5 mg three times daily (1.5 mg–maximum group). The dose-adjustment plan for riociguat is described in detail in Fig. S1 and the section on the dosing regimen in the Supplementary Appendix. Template | Weeklyplanner.website! Riociguat therapy was initiated at a dose of Sample Project Documents 1 mg three times daily, and the dose was adjusted according to the patient's systolic systemic arterial blood pressure and signs or symptoms of hypotension (final range, 0.5 mg to 2.5 mg three times daily).
The dose reached at the end of the 8+ Event Schedule Template | Weeklyplanner.website 8-week adjustment phase was considered to be the appropriate dose for the patient, and the patient continued taking the drug at Easy To Calculate Employee, that dose for 8+ Event Template, another 4 weeks. Sample Letter - 9+ In Pdf,! In the 1.5 mg–maximum group, therapy was initiated at a dose of 1 mg three times daily, and the dose was adjusted every 2 weeks to a maximum dose of 1.5 mg three times daily. Since no further increase in dose was allowed, patients in this group and those in the placebo group underwent sham adjustment of doses to maintain the blinding of the treatment assignments. | Weeklyplanner.website! The 1.5 mg–maximum group was included for exploratory purposes, to provide information about lower riociguat doses, and data from that group were not included in the efficacy analyses. Patients were seen at weeks 2, 4, 6, and 8 (during the dose-adjustment phase) and at week 12 (at the end of the Easy Spreadsheet To Calculate Keep maintenance phase). At each visit, clinical assessments and blood tests were performed. Patients who discontinued therapy for any reason were withdrawn from the Schedule | Weeklyplanner.website trial; these patients underwent an | Download Free, efficacy assessment at the termination visit and had no further efficacy assessments after withdrawal. 8+ Event Schedule! All surviving patients returned for a follow-up assessment of safety at 30 days.
All patients who completed the Sample Planning - 7+ Documents 12-week PATENT-1 study period were eligible to enter the 8+ Event Schedule Template | Weeklyplanner.website PATENT-2 long-term extension study. The primary end point was the change from baseline to Keep, the end of Schedule | Weeklyplanner.website week 12 in the distance walked in 6 minutes. Secondary efficacy end points included changes from baseline to the end of Sample Planning - 7+ Documents week 12 in pulmonary vascular resistance, N-terminal pro–brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class (an adaptation of the New York Heart Association functional classification), the time to Schedule Template, clinical worsening (as defined in the Supplementary Appendix), Borg dyspnea score (which ranges from - 9+ Word 0 to 10, with 0 representing no dyspnea and 10 maximal dyspnea), score on the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D, in which scores range from –0.6 to Template | Weeklyplanner.website, 1.0, with higher scores indicating better quality of life), and the Living with Pulmonary Hypertension (LPH) questionnaire (an adaptation of the - 7+ Pdf Minnesota Living with Heart Failure Questionnaire, with scores ranging from 8+ Event Schedule 0 to 105 and higher scores indicating worse quality of life). Adverse events and laboratory variables were assessed throughout the study and during the safety follow-up period. We calculated that with 250 patients in - 9+ Examples, the 2.5 mg–maximum group and 125 in the placebo group, the study would have 90% power to detect a least-squares mean difference in 8+ Event Template, the 6-minute walk distance of 25 m, at Implementation Plan Template, a two-sided significance level of 5%. The primary efficacy analysis was performed on data from the modified intention-to-treat population (all patients who underwent randomization and received at least one dose of the Schedule | Weeklyplanner.website study drug) ( Figure 1 Figure 1 Screening, Randomization, and Follow-up. The two patients who underwent randomization but did not receive a dose of the study drug (one in the placebo group and one in Template Templates, the 1.5 mg–maximum group) were ineligible for the study and 8+ Event Schedule Template | Weeklyplanner.website were randomly assigned in error by the investigator. The three deaths during follow-up (two in the 2.5 mg–maximum group and one in the placebo group) occurred in patients who withdrew from the study and died during the Plan Sample 30-day follow-up period. 8+ Event Template | Weeklyplanner.website! ). A per-protocol analysis was also performed (see the Supplementary Appendix). Values that were missing owing to withdrawal of Sample - 9+ a patient from the study or death were imputed as described in the Supplementary Appendix. The statistical analysis plan was identical to the plan in the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial 1 (CHEST-1). 8+ Event Schedule | Weeklyplanner.website! 4 Briefly, the primary end point and the secondary end points that were measured on a semicontinuous scale were analyzed by means of Nda For Software - Non | Custom analysis of covariance followed by a test of Schedule normality of the To Calculate Employee Pay And residuals and, if rejected, a nonparametric stratified Wilcoxon test.
Changes in the WHO functional class and the Borg dyspnea score were analyzed with the use of a stratified Wilcoxon test, and the time to clinical worsening was analyzed with the use of Schedule | Weeklyplanner.website a stratified log-rank test. Easy Spreadsheet To Calculate Employee Pay And! Secondary efficacy variables were tested with the use of a hierarchical testing procedure, in the following order: pulmonary vascular resistance, NT-proBNP level, WHO functional class, time to clinical worsening, score on the Borg dyspnea scale, EQ-5D score, and score on the LPH questionnaire (see the Schedule Template Supplementary Appendix). Pdf! Safety was analyzed descriptively. Adverse events during the Schedule Template study period included all adverse events that started or worsened from the time of administration of the Easy Spreadsheet Available Employee Keep first dose of the study drug until 2 days after administration of the last dose. Further details regarding the statistical analysis are provided in Schedule | Weeklyplanner.website, the Supplementary Appendix. From December 2008 through February 2012, a total of 443 patients were randomly assigned to receive placebo (126 patients), riociguat at Inspiration How To An Acting Resume, individually adjusted doses up to 2.5 mg three times daily (254 patients), or riociguat at individually adjusted doses capped at 1.5 mg three times daily (63 patients) ( Figure 1 ). The baseline characteristics of the patients were well balanced among the groups ( Table 1 Table 1 Baseline Demographic and Clinical Characteristics of the Patients. ). Idiopathic pulmonary arterial hypertension was the 8+ Event Schedule most common diagnosis, and the majority of Easy To Calculate Employee Pay And patients were in 8+ Event Schedule, WHO functional class II or III.
A total of 44% of the patients were receiving treatment with endothelin-receptor antagonists (primarily bosentan), and 6% were receiving prostanoid therapy (primarily inhaled iloprost); 50% were receiving no other treatment for pulmonary arterial hypertension. A total of 38 patients withdrew from the Project Planning In Word, study before week 12 ( Figure 1 ). In the 2.5 mg–maximum group, 75% of the patients were receiving the maximal dose at week 12, 15% were receiving 2.0 mg three times daily, 6% 1.5 mg three times daily, 3% 1.0 mg three times daily, and 2% 0.5 mg three times daily. The dose of the study drug was decreased in 31 patients (12%) in this group as compared with 11 patients (9%) in the placebo group. In the 8+ Event Schedule 1.5 mg–maximum group, 96% of the patients were receiving 1.5 mg three times daily at week 12. At week 12, the 6-minute walk distance had increased from Development Disclosure | Custom baseline by a mean of 30 m in the 2.5 mg–maximum group and had decreased by Template a mean of 6 m in Splendid Inspiration Write Resume 9 Acting, the placebo group (least-squares mean difference, 36 m; 95% confidence interval [CI], 20 to 52; P0.001), on Schedule the basis of an analysis of the modified intention-to-treat population with missing values imputed ( Table 2 Table 2 Change from Baseline to End of Week 12 in Primary and Secondary End Points and Nda For Software Development Disclosure | Custom Hemodynamic Variables. and Figure 2 Figure 2 Mean Change from Baseline in the 6-Minute Walk Distance. Mean (±SE) changes from baseline in the distance walked in 6 minutes during the 8+ Event Schedule Template 12-week PATENT-1 study period are shown in the group that received riociguat at a dose up to 2.5 mg three times daily as compared with the Easy Spreadsheet To Calculate Employee Keep placebo group. The data were analyzed in the modified intention-to-treat population without imputation of missing values; imputed values are provided at week 12. The number at each data point indicates the number of patients included in the assessment at that time point.
The least-squares mean difference in the 6-minute walk distance at week 12 was 36 m (95% CI, 20 to 52; P0.001). The last observed value (not including follow-up) was carried forward for patients who completed the study or withdrew; the 8+ Event Schedule worst value (0 m) was imputed in the case of death or clinical worsening without a termination visit or without a measurement at Template Sample - Apigram.com, the termination visit. ). The benefit with riociguat was similar (Table S1 in the Supplementary Appendix) in sensitivity analyses for missing data that used statistical methods for longitudinal data, as described in the Supplementary Appendix. The increase in the 6-minute walk distance in the per-protocol population (Table S2 in the Supplementary Appendix) was consistent with the increase in the main analysis. The treatment effect was consistent in several patient subgroups, including subgroups defined according to status with respect to treatment with additional agents for 8+ Event Schedule Template | Weeklyplanner.website, pulmonary arterial hypertension (Fig. S2 and Nda For Software Development - Non Disclosure Agreements | Custom Table S3 in the Supplementary Appendix). 8+ Event Schedule | Weeklyplanner.website! As anticipated, there was statistical evidence of heterogeneity of the treatment effect in subgroups defined according to WHO functional class; patients in functional class III or IV had a significantly greater benefit with riociguat therapy than did those in functional class I or II. Secondary End Points in the 2.5 mg–Maximum Group versus the Placebo Group. Pulmonary vascular resistance decreased by 223 dyn·sec·cm –5 in the 2.5 mg–maximum group, as compared with 9 dyn·sec·cm –5 in the placebo group (least-squares mean difference, –226 dyn·sec·cm –5 ; 95% CI, –281 to –170; P0.001) ( Table 2 ). Significant improvements in other hemodynamic variables, including mean pulmonary-artery pressure and Sample cardiac output, were also evident in 8+ Event Schedule Template, patients treated with riociguat ( Table 2 ). Implementation Plan Sample! Significant benefits were seen in the 2.5 mg–maximum group, as compared with the placebo group, with respect to Schedule | Weeklyplanner.website, other secondary end points, including NT-proBNP levels, WHO functional class, and score on the Borg dyspnea scale ( Table 2 ). There was also a significantly lower incidence of events indicating clinical worsening in Inspiration How To Resume, the 2.5 mg–maximum group than in the placebo group ( Table 3 Table 3 Clinical Worsening and 8+ Event Schedule Template Adverse Events. ). The Kaplan–Meier estimates of the Documents Pdf proportion of patients with clinical worsening are provided in Fig. S3 in the Supplementary Appendix. The EQ-5D score did not differ significantly between the 2.5 mg–maximum group and the placebo group (P=0.07).
On the Template | Weeklyplanner.website basis of the Of Resignation In Pdf, Word prespecified hierarchical testing procedure, the analysis of the 8+ Event Template | Weeklyplanner.website scores on the LPH questionnaire was considered to be exploratory (Table S4 in the Supplementary Appendix); there was a nominally significant difference between the 2.5 mg–maximum group and the placebo group in Available Pay And, that secondary outcome ( Table 2 ). End Points in the 1.5 mg–Maximum Group. The analysis of the 8+ Event Schedule Template | Weeklyplanner.website 1.5 mg–maximum group was exploratory, and data from Nda For - Non Disclosure that group were not included in the efficacy analyses. The results with respect to the primary and secondary end points in this group are shown in Table S5 in 8+ Event Template, the Supplementary Appendix. Safety Results in Easy Spreadsheet Available Pay And Keep, the 2.5 mg–Maximum Group and the Placebo Group. The adverse events that occurred most frequently during the study period are shown in Table 3 . The most frequently occurring serious adverse events were syncope (in 1% of the patients in the 2.5 mg–maximum group vs. 4% in the placebo group), worsening pulmonary hypertension (in 1% of the 8+ Event Schedule patients in the 2.5 mg–maximum group vs. 2% in the placebo group), chest pain (in 1% of the patients in both the 2.5 mg–maximum group and the placebo group), and right ventricular failure (in 1% of the patients in both groups).
Drug-related serious adverse events in the 2.5 mg–maximum group included three cases of syncope (in 1% of the patients) and single cases of increased hepatic enzyme levels, dizziness, presyncope, acute renal failure, and hypotension (in a total of Nda For Development - Non Disclosure 0.4% of the patients), and in the placebo group, single cases of 8+ Event diarrhea, presyncope, syncope, dyspnea, and worsening pulmonary hypertension (in a total of 1% of the Template Sample - Apigram.com patients). Eight patients (3%) in the 2.5 mg–maximum group and nine patients (7%) in the placebo group discontinued the study drug owing to adverse events. The following events leading to discontinuation of the study drug were considered by the investigator to be drug-related adverse or serious adverse events: in the 2.5 mg–maximum group, increased hepatic enzyme levels (serious), acute renal failure (serious), syncope (serious), esophageal pain and esophageal swelling, supraventricular tachycardia, hypotension, generalized edema, and neck pain; in the placebo group, diarrhea, syncope (serious), dyspnea, hypoxemia (serious), and worsening of pulmonary hypertension (serious). Deaths related to adverse events occurred in two patients (1%) in the 2.5 mg–maximum group (one each from sepsis and hemoptysis) and in three patients (2%) in the placebo group (one each from worsening anxiety followed by 8+ Event | Weeklyplanner.website acute respiratory failure, worsening pulmonary hypertension, and respiratory failure); none of the deaths were considered to be related to the study drug. A total of 396 patients (98% of the patients who completed the study) entered the Wedding Brochure | Download long-term extension study PATENT-2, in which the treatment assignments were concealed for 8+ Event | Weeklyplanner.website, the first 8 weeks and treatment was open-label thereafter. Wedding Template | Download Free Templates! Of these patients, 363 patients (308 of whom were still receiving treatment at a median of 441 days) were included in 8+ Event | Weeklyplanner.website, an interim analysis of Wedding | Download Free & Premium data collected up to April 2012. An exploratory analysis of the first 12 weeks of PATENT-2 showed further increases in the 6-minute walk distance in the 215 patients receiving up to 2.5 mg of 8+ Event Schedule Template | Weeklyplanner.website riociguat three times daily. A mean (±SD) increase of 53±62 m over Sample the baseline distance in PATENT-1 among these 215 patients was observed at week 12 of PATENT-2. The same group had had an 8+ Event | Weeklyplanner.website, increase of 36±54 m at week 12 of PATENT-1.
In this trial, riociguat significantly improved exercise capacity in patients with pulmonary arterial hypertension. This benefit was consistent in patients who were receiving endothelin-receptor antagonists or prostanoids and in those who were receiving no other treatment for Available Employee Pay And, the disease. Riociguat also significantly and consistently improved a range of secondary efficacy end points, including pulmonary hemodynamics, WHO functional class, and time to 8+ Event Template | Weeklyplanner.website, clinical worsening. Although some studies suggest that the Design Inspiration 6-minute walk distance has modest validity as a surrogate end point for Schedule | Weeklyplanner.website, clinical events, 8 it is the most frequently used primary end point in randomized, controlled trials involving patients with pulmonary arterial hypertension, 9 is an independent predictor of death, 10 and correlates with changes in functional status and Software Development Agreements hemodynamic variables and with survival. 11 The overall difference in the 6-minute walk distance with riociguat as compared with placebo (36 m) at 12 weeks is Schedule Template, consistent with the increases observed in previous studies of other medications for Examples Word, the treatment of 8+ Event Template | Weeklyplanner.website pulmonary arterial hypertension (16 to Sample, 59 m). 8+ Event Schedule | Weeklyplanner.website! 12-17 Furthermore, these improvements were maintained during the first 12 weeks of the long-term extension study. The improvement in the 6-minute walk distance with riociguat as compared with placebo is also within the range of How To Write thresholds that have previously been reported to represent a clinically relevant change (31 to 42 m).
8,18,19 However, a large proportion of patients in 8+ Event Template | Weeklyplanner.website, PATENT-1 had WHO functional class II symptoms at baseline and Development - Non Disclosure | Custom a baseline 6-minute walk distance that was relatively long; thus, this population had less advanced illness than did the population in many previous studies. Indeed, there was statistical evidence from Schedule | Weeklyplanner.website a subgroup analysis that WHO functional class influenced the Plan beneficial effect of riociguat on the 6-minute walk distance — a finding that was anticipated from 8+ Event Schedule previous observations 13,15 — suggesting that the Design Resume 9 Acting benefit with riociguat is more likely to be clinically important in patients with WHO functional class III or IV symptoms than in those with class I or II symptoms. The inclusion in PATENT-1 of patients who were receiving endothelin-receptor antagonists or prostanoids also warrants consideration, since the clinically relevant thresholds for 6-minute walk distance may not be accurate for patients receiving background therapy. Schedule Template | Weeklyplanner.website! Another study, the Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) study, 15 closely resembled PATENT-1 with respect to both the Sample - 7+ Documents In Word, Pdf patient population and 8+ Event the study design, since the PHIRST study included both patients who had received or were currently receiving no treatment for the disease and patients who were receiving endothelin-receptor antagonists. However, in the PHIRST study, patients receiving background endothelin-receptor–antagonist therapy did not have significant improvements in the 6-minute walk distance, whereas in PATENT-1, riociguat improved the 6-minute walk distance in Available Pay And Keep, both patients who were receiving no therapy for the disease and patients who were receiving endothelin-receptor antagonists or prostanoids. In PATENT-1, riociguat was associated with consistent improvements across a range of 8+ Event clinically relevant primary and secondary end points, including 6-minute walk distance, pulmonary vascular resistance, and time to clinical worsening — improvements that were not seen in some previous trials.
Delays in clinical worsening are considered to be clinically relevant, 20 and the delay in clinical worsening that was observed in PATENT-1 was consistent with the greater number of patients with improved or stable WHO functional class in the group receiving riociguat at a dose up to 2.5 mg three times daily than in Nda For Software Disclosure | Custom, the placebo group. The hemodynamic improvements observed with riociguat require further characterization but could be related to disease-modifying effects, such as antifibrotic, antiproliferative, and antiinflammatory effects, that were observed in preclinical studies. 8+ Event Schedule | Weeklyplanner.website! 21-25 In addition, the increase in cardiac output was reflected by a decrease in NT-proBNP levels, which could be indicative of Sample Letter - 9+ In Pdf, Word decreased right ventricular afterload. An obvious limitation of PATENT-1 was the lack of 8+ Event follow-up efficacy measurements in patients who withdrew from the Template study. However, sensitivity analyses that were performed with a variety of approaches to 8+ Event Schedule | Weeklyplanner.website, impute missing data suggest that the results are dependable despite these losses to follow-up.
Another limitation was the exclusion of patients with pulmonary arterial hypertension associated with human immunodeficiency virus infection, schistosomiasis, and chronic hemolytic anemia. Patients who were receiving treatment with phosphodiesterase type 5 inhibitors or intravenous prostanoids were also excluded from PATENT-1, and the effect of riociguat in Splendid Design How To An Acting Resume, such patients is 8+ Event Schedule, unknown. In conclusion, riociguat significantly improved the 6-minute walk distance, as well as pulmonary vascular resistance and several other secondary efficacy end points, in patients with symptomatic pulmonary arterial hypertension who were receiving no other treatment for the disease or who were receiving endothelin-receptor antagonists or prostanoids. Supported by Bayer HealthCare. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank Mike Kenward, Ph.D., from the London School of Hygiene and Tropical Medicine for advice on the missing-data sensitivity analysis.
From the University of Giessen and Marburg Lung Center, Giessen, member of the German Center for Lung Research (H.-A.G., F.G.), Center for Pulmonary Hypertension, Thoraxclinic, University Hospital Heidelberg, Heidelberg (E.G.), and Global Clinical Development, Bayer HealthCare, Wuppertal (A.F., D.N.) — all in Germany; Department of Medicine, Imperial College London, London (H.-A.G.); Department of Wedding Brochure Template | Download Free Experimental, Diagnostic, and Specialty Medicine, Bologna University Hospital, Bologna (N.G.), and Global Clinical Development, Bayer HealthCare, Milan (M.O.K.) — both in Schedule, Italy; Assistance Publique–Hopitaux de Paris, Service de Pneumologie, Hopital Bicetre, Universite Paris-Sud, Laboratoire d'Excellence en Recherche sur le Medicament et Innovation Therapeutique, and INSERM Unite 999, Le Kremlin–Bicetre, France (M.H.); State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (Z.-C.J.); St. Vincent's Hospital, Sydney (A.M.K.); Center for Pulmonary Vascular Disease and Lady Davis Institute, Jewish General Hospital, McGill University, Montreal (D.L.); and University of California, San Diego, La Jolla (L.J.R.). Address reprint requests to Software | Custom, Dr. Ghofrani at the Department of Internal Medicine, Medical Clinic II/V, University Hospital Giessen and Marburg, Klinikstr. 33, Giessen 35392, Germany, or at [email protected] The full list of investigators and Template trial committees of the Pulmonary Arterial Hypertension Soluble Guanylate Cyclase–Stimulator Trial 1 (PATENT-1) Study Group is provided in the Supplementary Appendix, available at Inspiration Write An Acting, NEJM.org.
Galie N , Hoeper MM , Humbert M , et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for Schedule Template, the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and Development - Non Disclosure Agreements the European Respiratory Society (ERS), endorsed by Template the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 2009;30:2493-2537[Erratum, Eur Heart J 2011;32:926.] Schermuly RT , Ghofrani H-A , Wilkins MR , Grimminger F . Mechanisms of disease: pulmonary arterial hypertension. Nda For Development! Nat Rev Cardiol 2011;8:443-455. Benza RL , Miller DP , Barst RJ , Badesch DB , Frost AE , McGoon MD . An evaluation of long-term survival from 8+ Event Template time of Brochure | Download Free Templates diagnosis in pulmonary arterial hypertension from the REVEAL registry. Chest 2012;142:448-456. Ghofrani H-A , D'Armini AM , Grimminger F , et al. Riociguat for the treatment of 8+ Event chronic thromboembolic pulmonary hypertension.
N Engl J Med 2013;369:319-329. Grimminger F , Weimann G , Frey R , et al. First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension. Eur Respir J 2009;33:785-792. Stasch JP , Pacher P , Evgenov OV . Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease.
Circulation 2011;123:2263-2273. Ghofrani H-A , Hoeper MM , Halank M , et al. Riociguat for chronic thromboembolic pulmonary hypertension and Nda For Development Agreements pulmonary arterial hypertension: a phase II study. Schedule | Weeklyplanner.website! Eur Respir J 2010;36:792-799. Gabler NB , French B , Strom BL , et al. Validation of 6-minute walk distance as a surrogate end point in Sample Project Planning Documents Pdf, pulmonary arterial hypertension trials. Circulation 2012;126:349-356. McLaughlin VV , Archer SL , Badesch DB , et al. Template | Weeklyplanner.website! ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the Sample Project - 7+ Pdf American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association.
Circulation 2009;119:2250-2294[Erratum, Circulation 2009;120(2):e13.] Miyamoto S , Nagaya N , Satoh T , et al. Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension: comparison with cardiopulmonary exercise testing. Am J Respir Crit Care Med 2000;161:487-492. Galie N , Manes A , Negro L , Palazzini M , Bacchi-Reggiani ML , Branzi A . A meta-analysis of 8+ Event randomized controlled trials in pulmonary arterial hypertension. Nda For Development Disclosure Agreements | Custom! Eur Heart J 2009;30:394-403. Barst RJ , Rubin LJ , Long WA , et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 1996;334:296-301. Galie N , Ghofrani H-A , Torbicki A , et al. Sildenafil citrate therapy for 8+ Event Template, pulmonary arterial hypertension.
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The Real Reason You Shouldn’t Put Your Address on Your Resume. When you put your address on 8+ Event Template, your resume, recruiters know exactly where you live. This matters because a person with a one-hour commute has to earn 40% more money to be as happy with life as someone who walks to the office (more here). Recruiters Calculate How Long Your Commute Is. You might not have thought about it, but in-house recruiters know that people with long commutes have more stress and often eventually quit “because of the commute.” If you quit, they don’t look good, and they have to replace you. | Download Templates. That’s more work, with no more money, for them. So — address on 8+ Event Schedule | Weeklyplanner.website, resume? They do the math. Sample Planning Documents. If you live too far away, you don’t get an interview.
Instead of giving your address on your resume, give your current or most recent employer’s city location, like this: The Coca-Cola Company, Atlanta, GA (if you work at the mother ship) The Coca-Cola Company, Oakland, CA (if you work at a branch office) Sharing your employer’s location places you in a broad metropolitan area. It gives recruiters enough information to know you’re local without sharing that you’re not local enough.
Note: Per a helpful comment below, you can see how this looks on a full resume here. Beyond the push to get a job, think about the stats in this post’s opening paragraph when you decide where to live and Schedule | Weeklyplanner.website where to apply for work. Working close to Brochure Template Free & Premium Templates home can make you and your family happier and prevent you from Template | Weeklyplanner.website looking like a job hopper on your resume. I write executive resumes and Inspiration How To Resume LinkedIn profiles. Save time. Get hired. Schedule Template | Weeklyplanner.website. Email me at Design How To Write An Acting 9 Acting, [email protected] for more information. Updated June 2017.
Donna, as usual your research and reporting on a topic is spot on, however there is a consideration that should be seen by job seekers before changing their tactics about publishing their address: It may also signal that there is something to hide and immediately disqualify the resume. If I am the corporate recruiter and daily fight the company bureaucracy as well as candidates trying to game the system, the blind resume is almost always immediately discarded. If I am an outside recruiter trying to find the best fit, the address is less relevant than the qualifications to do the job and 8+ Event Schedule Template | Weeklyplanner.website we will discuss the requirements for relocation or commuting honestly before moving forward. Brochure Free & Premium. In both cases, recruiters generally have the interests of the candidate in mind. 8+ Event | Weeklyplanner.website. Believe it or not, it is not always an adversarial relationship that requires stealth and deceit on either side to Implementation Sample - Apigram.com make a connection and a good hire. In years past, I was concerned about candidates who didn’t provide their addresses for | Weeklyplanner.website, just the reasons you outlined above.
Now, as concerns about identify theft have become realistic, and Nda For Software most communication is electronic (thus no need to snail mail applicants for any reason), I think people can provide general metropolitan area information and be OK. It’s definitely a “best resume practice” in Schedule | Weeklyplanner.website, transition. People have to balance between the pros and cons on so much of the Nda For Disclosure information they include on their resumes. In the end, they have to weigh what seems best for them and 8+ Event Template | Weeklyplanner.website make an Implementation Plan informed decision. I appreciate you raising this perspective for people to consider. I’m curious to hear what other people think about this topic! Valid points.
How would you approach applying for jobs in a different city? The same question came up on 8+ Event Template, LinkedIn this morning. Here’s what I wrote: I recently worked with a resume client who wanted to Implementation Template move across the U.S. He was willing to pay his own relocation costs. We put his aspirational city location in 8+ Event Schedule Template, his contact info and showed his current employer’s city location. We also put a line at Design Inspiration How To Write 9 Acting, the bottom of his resume that said, “Willing to relocate to [desired location] at own expense.” It worked. I usually just put the 8+ Event Schedule city / state on clients’ resumes, like this:
Oakland, CA | 510-000-0000 | [email protected] | LinkedIn address. That way, it shows the job seeker is local, but doesn’t go into unnecessary detail. Sample Project - 7+ Pdf. Kathy. Thank you for this. My concern is Schedule, that a recruiter might think Oakland is “not local enough” for a job in their Bay Area location.
That’s why I avoid giving my client’s home location and use their employer’s location instead. As I’ve never seen a resume without a full home address front and - 7+ In Word, Pdf centre, it’s most intriguing to 8+ Event Template | Weeklyplanner.website give this a re-think. And come to Implementation - Apigram.com think of it, it’s surely a vestige of snail mail times that we so unthinkingly offer up the exact mailing address of 8+ Event, our domiciles to all and sundry – surely workarounds like the one Donna is Project Planning Documents, suggesting here will become the norm soon enough! But for those currently unemployed, Donna, do you really suggest using the address of their last employer at the top of the document? I’d be worried this could be unnecessarily puzzling, so not sure I could sell my clients on the idea. Thank you for your clarifying question. I added a link to a sample resume above. All good thoughts but even a city or for that matter a State may be grounds for 8+ Event Template, “Commute Discrimination”! I always suggest that if this was the dream job would you be willing to Implementation Plan Sample re-locate and if so put that information at the end of a Career Summary. Thank you for this.
I don’t get that from an employer’s location. It just tells me they manage to 8+ Event get themselves there from somewhere. Who knows? Maybe my client’s location is closer to home for - Non Agreements | Custom, a candidate! It’s always interesting to Schedule Template see how other people interpret information. That’s one of my favorite aspects of blogging. It makes me realize how uncertain anything that seems certain really is! I have not used a physical address on my personal resume for years, and I have advised clients that it is no longer a requirement to Easy Spreadsheet Available Pay And Keep have it there (some choose to include it, and that’s fine) for the reasons you’ve cited above, as well as the concerns with identity theft, etc. Employers rarely use snail mail to communicate with candidates these days, so the 8+ Event Schedule address doesn’t really add value–it provides another chance to lose out on Software Development - Non Agreements | Custom, an opportunity for reasons other than qualifications and ability to do the job. It also gives a little bit more real estate on the resume, which can be used to 8+ Event Schedule Template | Weeklyplanner.website provide info that does add value, such as social media profile links.
Wearing my recruiter hat for Sample Project Planning Documents In Word, Pdf, a moment, I am MUCH more interested in 8+ Event Schedule, your LinkedIn profile than your home address. If as recruiters the objective is to identify the best possible candidates for the job, then we ought to be looking for more ways to include good candidates than somewhat arbitrary (in some cases) reasons for rejecting them. Awesome Warren. Thank you for the wonderful “guest post!” Donna. I don’t care about a physical address when I’m reviewing resumes. I’m not a recruiter, but I’m involved in recruiting. I do care about email, phone, and time zone though.
And i care if you have a decent internet connection. My company hires remotely, so candidates don’t have a commute to worry about, at least for the positions I’m involved in hiring for. I recognize that many people don’t yet work remotely and that there are jobs that won’t ever be distributed either. Wedding Template | Download Free Templates. But from my own point of view the concern about an exact physical address seems dated. If the person is Schedule Template | Weeklyplanner.website, hired though, we do need that for records, to ship stuff to, etc. When review resumes I want to see contact info: email, phone, name, city.
I want to Splendid Design Write see what you’ve done that’s notable, and your skills, and 8+ Event Template | Weeklyplanner.website that you’re legal to Sample Project - 7+ In Word, work in my country. It’s amazing the number of resumes that come in 8+ Event Schedule | Weeklyplanner.website, that don’t satisfy those basic requirements! I don’t need to see a link to your dancing lessons (true), nor do I need to know your married or not, or have kids or not. Thank you Malcolm. Easy Employee Pay And Keep. Donna. I have been working remotely for a company based in 8+ Event Schedule | Weeklyplanner.website, another state for four years. The nearest major city is about a 35-45 minute commute. In the past, interviewers have remarked on what a long commute it is from Small Town, USA. Letter Word. What would be the best way to handle the ‘no address’ on a new resume? That’s a tough one Jesse.
Like Minh (see below), I would go with the 8+ Event Template | Weeklyplanner.website location that shows me closest to prospective employers. Sample Documents. Thank you, Donna. What if you are currently commuting to work, and your current job is Template, far away from that which you want to be at? For instance, I currently live with a friend an hour away from an apartment I still have a lease on Brochure Template | Download & Premium, to commute an hour to go to work, but I want to apply to a job that is within commuting distance of Schedule | Weeklyplanner.website, my apartment that I still have the lease on. This makes the jobs I am applying to hail from cities that are 2 hours away from my current job location. What should I do? Good question Minh.
In that case, I would use the Sample Letter Of Resignation - 9+ In Pdf, Word city were your leased apartment is because it’s closer to potential employers than your current employer. Thank you, Donna. Would you REALLY put “US Resident Alien.” on a resume? Seriously? Good question. I have placed many people from Schedule Template other countries in the U.S. and the EU.
In those cases, employment eligibility is often a concern. The questions go like this: 1. Can we legally employ this person here? 2. If they’re not a citizen, are they otherwise already legally entitled to work here? 3. Sample. If not, how long would it take (extremely important) and how much would it cost (less important)? Because of Schedule Template, this, when there is any potential question about someone’s work eligibility, and Design Inspiration Write they are fully eligible, I spell it out on the resume. Not doing this could easily cost them the opportunity to 8+ Event interview.
In the case you ask about, U.S. Resident Alien, this legal term shares clear information that the individual has full status to work in the U.S. long-term without any visa, time, or cost issues. Thank you for asking about this! Donna, I stopped using a full street address on my clients’ resumes more than a year ago, with no problems reported. Implementation - Apigram.com. As others have pointed out, the job search isn’t done by 8+ Event | Weeklyplanner.website snail mail anymore. Providing your street address doesn’t add any value to the process.
It does, however, raise concerns about personal security and Software Development Disclosure Agreements | Custom identity theft. And one other concern I didn’t see mentioned elsewhere: the practice of recruiters running your street address through a real estate database like Zillow to Schedule | Weeklyplanner.website determine home value–and use that as a factor in negotiations. Sounds bizarre, I know, but my contacts in HR and recruiting were familiar with the tactic. They actually show previous purchase prices on Zillow and other Internet locations…which would let a company estimate your mortgage…smart background research for them to do…with a TOTAL creeper feel to Splendid Inspiration How To Write it. Thank you for the heads up on this Robert. Donna. Just want to thank you again for your input earlier on twitter, as I came across this article after the 8+ Event Template | Weeklyplanner.website fact. Nda For Software - Non Disclosure | Custom. Sorry about that. Next time, I have a resume or career issue I’m heading to your blog first before conducting a Google search.
I have to Schedule agree with you about the fact that a job candidate’s home address takes up essential space on a resume, that can be better used on Nda For Software Disclosure | Custom, value added material. In my case, it was the home address line that was the only factor holding me back from creating a concise one-page resume. I suppose it was a no-brainer to leave it out, but I just had to hear it from a Pro. Donna, you provide such a valuable service for us job/career seekers. Can’t thank you enough. It seems down the 8+ Event | Weeklyplanner.website road when I am financially ready to relocate to Dallas from San Diego I’ll be contacting you directly to make use of your services to Agreements butcher or polish up my resume and LinkedIn profile.
Simply impressed with your background, accomplishments, and kindness of helping those in 8+ Event Schedule, need. Wow, Shel, thank you! What a lovely way to start the week. Good post. When I create CVs for Sample, my customers, I usually create one with a full address and one with just the town or county. The latter is for uploading online. 8+ Event | Weeklyplanner.website. Security is a major issue and I recommend giving too much personal data when posting online. Thank you David.
Donna. They will find out Brochure Template | Download & Premium, your address someway. It is 8+ Event Schedule Template | Weeklyplanner.website, always best to | Download & Premium put your full information on a resume and not lie or withhold any information. They certainly can if they want to Caleb. 8+ Event Schedule. However, they probably won’t do it before they make their interviewing decision. Once recruiters and hiring managers know more about Easy Spreadsheet Employee Pay And a person, positives often outweigh negatives. There aren’t many clear answers in job search so I appreciate your perspective. Looking at issues from Template multiple angles helps job seekers evaluate where they fit and decide on a course of action. What if your current employer and Spreadsheet To Calculate Employee home are in the same town? I’m in that situation, and applying for jobs in Boston, about an 8+ Event Template hour away. Ed, I would probably show my employer’s location and leave mine off.
That puts you in the vicinity of Boston without definitively saying that you live an Design How To Write hour away. Donna. Interesting discussion. One can sway to either side given the Schedule Template circumstances. Please note, however, that a high percentage of employers request that resumes, cover letters and other relevant documents be uploaded online. The online system then extracts the information from the uploaded document (e.g, resume) and populates required data fields (e.g., name, address, phone, email, dates of employment, titles, employer name, location, duties, etc.). Of course one can view the employer’s online application web address for the recognized secure prefix URL protocol that starts with https:// in the hopes that it is in Planning - 7+ Documents Pdf, fact a safe entry portal. So unless you are sending your resume to an HR department or other recipient email address, the Schedule | Weeklyplanner.website street address will be required from the initial application (resume). And finally, I have worked a relocated job and Sample - Apigram.com telecommuting across the country.
Please note that those jobs clearly indicated such employment options. This highlights yet another reason it’s good to 8+ Event Template network one’s way into Template Sample job opportunities and avoid the applicant tracking system until after an interview has been secured.
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Analysis of Italian novel I'm not Scared. Extracts from this document. The book being titled I'm not scared is very appropriate as the common theme of the Schedule, book is Project Pdf orientated around many characters facing fears and overcoming them or giving in to them. Furthermore the progression of the story is determined by characters not being scared. The book is based in 1970s Italy. 8+ Event Schedule Template! More specifically in an isolated village named Acqua Traverse.
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Those texts might be translated by someone else who knows that language and the comparatist can use that translated text to solve his/her purpose. 8+ Event | Weeklyplanner.website! So one can say that: a. Each one of them comparative literature and translation are interconnected. b. A common man can come closer to the major writers of different fields. c. Brochure Template | Download Free & Premium! With the medium of translating literature from distinct text or languages one can figure out its sociology, philosophy, psychology as well as all their culture. d. 8+ Event Schedule Template! Either translation or through comparison the problems of particular area’s people will analysed. e. With the help of translation a text become able to get a wider range of readers. Comparative literature is a discipline dedicated to the study of literature without national and linguistic barriers. The student of comparative literature study problems in genre, mode, literary period or movement. Project Planning! The comparatists probe the mechanics of literary forms and engage themselves in the analysis of existing theoretical and critical approaches and the formulation of necessary critical distinctions of Schedule Template | Weeklyplanner.website equal importance. The comparatists also deal with the questions of interaction between literature and other arts and disciplines.
The comparatist may study the political, social and an intellectual context of literary emphasis is preserved. Nda For - Non! In other words, the main objective of the study of comparative literature is the proper appreciation of literature in a larger perspective, involving more than one literature and specially those growing across the national boundaries. In a multilingual country like ours we have two basic objectives for studying comparative literature. No doubt the role of translation in comparative literature is very important. It becomes more valuable in today’s world when the Template, whole world has become a global village. With the advancement of technology people living in Wedding Brochure Template | Download & Premium Templates, different countries with different languages come closer to each other. Although there is a one international language, English, which is the common source of 8+ Event Template | Weeklyplanner.website communication between people but still there is a problem in the study of literature as literatures is Template Sample - Apigram.com usually written in regional languages or languages of that particular countries such as France’s literature is in French and literature of 8+ Event | Weeklyplanner.website Russia is in Russian language. It is not compulsory that every comparatist will know the all languages. So there is need of Sample Letter Word translation by 8+ Event Template | Weeklyplanner.website which a comparatist can read and Nda For Software Disclosure Agreements understand that literary works which are not in his/her own language. With the help of translation we become familiar with the customs, dress code, and culture of other countries.
In short it can be said that translation plays a great role in comparative literature. We can even say that comparative study of literatures from different languages, cultures and sociocultural backgrounds is not possible. So translation occupies a special place in comparative literature. In this age of globalization comparative literature as a subject is getting more and more popularity. But there is no one who is perfect in all the languages. So translation has played a very important role to understand the literature culture of different languages without which we cannot do a comparative study of various literary works written in different languages. So Comparative literature is a tree with translation as its most important branch. 1. What is Translation? Translation is the transformation of a text from one language into another. Though the word translation and elucidation are frequently used exchangeable, by firm description, translation denotes to the transcribed language, and understanding to 8+ Event Schedule the spoken word.
Translation is the act of construal of the denotation of a text, and later construction of a comparable text, also entitled a translation, that passes the exact content in target language. The text or a work to be translated is termed the source text, and the language it is to be translated into is called the target language. Translation must take into Nda For Development Disclosure | Custom account brakes that include context, the rules of grammar of the two languages, their writing conventions, and their idioms. A common misconstruction is that there exists a simple word-for-word parallelism between any two languages, and that translation is a straight forward mechanical process. 1.1 History of Translation.
The necessity for translation has existed since time ancient and translating important literary works from one language into others has donated ominously to the growth of world culture. Ideas and customs of one culture have continuously progressed and got adjusted into other cultures through the works of | Weeklyplanner.website translators. Implementation - Apigram.com! The history of Schedule Template | Weeklyplanner.website translation is associated to the history of the often unseen cross cultural exchanges of the world. Thoughts and conceptions from the East notably India, Iraq and China have determined the Western culture since as early as sixth century B.C. when business ties were first instituted between Mediterranean countries and India. Many curative theories of Galen and Plato of Greece had significantly influence from those of India.
Many of the scientific and Nda For Software philosophical works of ancient Greece were extracted into Arabic as early as ninth century A.D. This knowledge spread via Spain to Europe which was a mostly a Muslim country then. The scholar of Schedule | Weeklyplanner.website translators of Toledo in Spain set up by Alfonso VI of Leon and Castile in 1085 AD was given responsibility for translations from Arabic to Latin and Available Pay And Keep then to Spanish these technological and scientific work which afterward led to the European Renaissance. In spite of their main contributions, early translators have repeatedly persisted unfamiliar or in the background and the recognition due to them have not been recognized. They have done their work with conscientious exertions in spite of many contravenes that have spotted in history.
Translators have enabled sacred books like the Bible written in esoteric languages like Latin to be understood by ordinary people by translating them into more common languages without depending on Schedule | Weeklyplanner.website, a few clerisy bishops to explain what they contained. Few translators also had to Wedding Brochure | Download & Premium Templates pay with their lives for Schedule | Weeklyplanner.website doing it like the well-known Bible translators William Tyndale who was caught and put to death in Implementation Plan Template, Holland by the king in 1536 for translating the Bible from its original languages into the common language of English. It was believed that Chinese monk Xuanzang have translated 74 volumes of Buddhist sacred text which was belong from India in to Chinese in 8+ Event Schedule Template, 645 AD. One of the Implementation Plan - Apigram.com, most former preserved translations of significant effort in English is possibly the Schedule, translation of the Bible around 1100 AD. Letter Of Resignation Examples! British translator Constance Garnett made the translating school pleased by her vivid translations of Russian classics containing those of Schedule Tolstoy, Chekhov, Gogol, Turgenev, and Nda For Development - Non Disclosure Agreements Dostoyevski in Template | Weeklyplanner.website, late 19s.
One more renowned translator is Gregory Rabassa who has translated numerous Latin American fictions into English. Dr. Arthur Waley is one of the world’s foremost translators of the Template Sample, 20th century of 8+ Event | Weeklyplanner.website Japanese and Chinese literature into Wedding Brochure Template | Download Free English. Further Gladys Yang translated many Chinese classics into English over the last fifty years. Translation has played an Template, important key role in Easy Available Employee, the improvement in culture at world level. Schedule | Weeklyplanner.website! It is simple to think of culture as nationwide and Plan Template Sample - Apigram.com completely distinct. If we commence to observe the effect of literary translation, the assumption of communication besides anything so limited by geographical location is clear. A history of world culture from the Template | Weeklyplanner.website, viewpoint of translation discloses a continuous movement of forms and ideas, of cultures regularly absorbing new inspirations because of the Project Planning In Word,, work of translators.
It dispels the supposition that everything begins in the West and weakens the idea of inflexible boundaries between West and East. India, Spain, China, and Iraq have in different ways shaped the culture of Europe. India formed ties with the Template | Weeklyplanner.website, Mediterranean in the 6th century BC and Nda For Software - Non Agreements medical theories found in Greek intellectuals like Galen and Schedule Plato initiated from India. In 9th and 10th century Baghdad, the philosophical and Spreadsheet Available To Calculate Employee Pay And scientific works of Earliest Greece were translated into Arabic and this learning disseminate to 8+ Event Schedule Europe via Spain which was virtually a Muslim country from the early 18th century for 400 years. The transmission extended it highest through the School of Toledo where translations were translated from Arabic to Latin and afterward to Spanish in order to enable the technological and scientific development for the Renaissance age. A history of translation charts these connections. They may be main cause in violent historical controversies and - 9+ Examples imperial increases but it is 8+ Event | Weeklyplanner.website never a simple procedure of translation for appropriation. A very few of the history of translation is well-drafted – the Nda For Software - Non Agreements | Custom, translation of the Bible, the work of missionary, the specialist translators in India – but there remains huge unknown dominions.
Researchers have recently begun to write about the role of individual translators and their translation. Translators like Gregory Rabassa in the United States or Constance Garnett in Template | Weeklyplanner.website, England have been responsible for transforming writing in English by their own translations of Spreadsheet To Calculate Employee Pay And Keep Russian and Latin American literature. In the raise of new political liberation in Eastern Europe have come translations of best-selling American and English writers. Template | Weeklyplanner.website! The history of translation is the history of the important but often not seen intersection point in world culture. Translation was an esteemed activity in Britain in the 18th Century, and the field was separated into two completely different areas: translation from translation from modern languages (French, German, Italian and Spanish) which was one of the few literary genres open to women and the older one that was the classics (focusing on Latin and Sample Project Pdf Greek authors) which was a male-dominated territory, and Yet, there were some significant exceptions in the area of the classics. It was the 8+ Event Schedule, central position occupied by Splendid How To Write An Acting Translators and their work in translation theory: translation studies has been progressively paying attention to their vital mediation in recent years. Instead of the fact that the 8+ Event Schedule | Weeklyplanner.website, communicative purpose of translation activities is the central engrossment of this method, Hans Vermeer has fetched attention to the degree of freedom, on the one hand, and of responsibility, on the other, which bears on language mediators (Vermeer 1998: 54). Translators are said to be the experts who should plan and implement those strategies which allow them to achieve their objective, i.e. their possibilities.
This ideas takes translators to the Centre of the stage, and yet it also made them busy in a certain amount of risk. Thus, they were the translators who had made important contribution over the centuries in broadcasting of Free & Premium ideas and information to a larger audience, in shaping of cultures and in 8+ Event Schedule Template, a sense helped unite the world. 1.2 Need and scope of Translation. In a huge nation like India, where countless regional changes in culture and behaviour obtain, and the many languages hold their unique origins and Spreadsheet To Calculate Pay And identities, it is impossible to hold an elaborative and Template continuous communication between various divisions of the country on a national as well as at - 9+, international scale. There couldn’t be the accurate meaningful responsiveness of the country-s total literary act. Schedule Template! The output without such mutual communication through the means of How To Resume 9 Acting translation. Translations of the known works of Indian literary creators like Tagore, Premchand etc… been effectively accepted and their writings have been read and enjoyed in all parts of India as well as outside of India. There has, however, been no organized effort to take up the significant works of each area and present them in a commonly understood language.
Books which has fusion has planned to publish a collection of literary work of English translations of modern short stories written in the distinct Indian languages, with the intention of getting the people together of India on one platform in order to make Indian literature available in India as well as the other parts of the world. 8+ Event Schedule | Weeklyplanner.website! There were so many translation occurred in the field of Sample Project Documents In Word, literature, the work which did not get recognition later after translation they achieved name and fame in India as well as in 8+ Event Schedule, other countries. Therefore, it was a required to spread literature of specific nation to Nda For Software - Non other nations through the medium of translation. 2. Types of Translation. As many experts were engaged in the field of translation, therefore they were having their own styles, methods, or techniques while translating any piece of translation. It was also found that they were using different style which has some kinds of variation in translation where practically one may find their own characteristics and forms.
Some types of translation are found out because of the variances and likenesses of the source structures, unlike types of 8+ Event | Weeklyplanner.website text that are going to be translated and various intention of translation. According to Newmark he said that translation techniques connect the whole texts, translation used for sentences and the smaller units of each language.  Roman Jakobson in Hatim and Munday brings an important differentiation between all three types of written translation : 1) Intralingual translation, the same language convey its meaning in the form of rewording or paraphrase, in order to achieve its meaning, 2) Interlingual translation, which mainly focuses to such translation which was carried out from one language to Splendid Design Inspiration Write An Acting 9 Acting another, 3) Intersemiotic translation, this kind of translation deals with verbal sign by | Weeklyplanner.website non-verbal sign for example audio- visual images like music or pictures. According to Nababan the kinds of translation, such as word for word translation, literal translation, dynamic translation, pragmatic translation, free translation, , aesthetic-poetic translation, ethnographic translation, linguistic translation communicative translation and semantic translation . 1. The Process of Translation. The procedure of translation can be well-defined as the activity carried out by the translator of Project Planning Documents Pdf translation, and the process which is 8+ Event Schedule | Weeklyplanner.website used by the translator as a kind of user manual in order to guide in translating from source text from into the target language. The process of translation contains mainly three steps, step one is to analyse texts where the translator analysed certain key aspects like structure of grammar, meaning of the words etc. of source language, step two is to transfer in which the translator focuses on the material of the source text and the target text which can be transferred based on the mentality of the translator, and step three is to restructured in order to get the exact message and make a new creation of the source language into target language.
2. Translation Equivalence. With the reference to oxford dictionary equivalence is exactly equivalency or replaceable in valuate, quantity, importance, etc.  Vinay and Software Disclosure Agreements | Custom Darbelnet as cited in 8+ Event Schedule Template, Munday, said that “equivalence denotes to - 7+ example where languages depict the equal situation by 8+ Event Schedule Template | Weeklyplanner.website unlike rhetorical or constructive/ structural means” . Equivalence stands for the concept of equality, sameness and similarity; it has the equal or a similar cause or meaning in translation. Nida also defined types of equivalence, which are also named two basic orientations of translation : 1. Formal correspondence. It emphases on the message itself, in To Calculate Keep, both of 8+ Event Schedule Template content and form. Brochure Template & Premium! Once it is seen that the content in Template, the receptor language should fit as closely as possible the unlike components in the source language. 2. Dynamic equivalence. It is the rationale of equivalent effect, where the Nda For Software Development - Non Agreements | Custom, connection between receptor and message should be considerably the same as that which laid between the 8+ Event Template | Weeklyplanner.website, original receptor and the message. The objective of the dynamic equivalence is getting the nearest natural equivalent to the source message. This receptor oriented method regards changes of grammar, of words, and of cultural acknowledgment to be important in order to attain naturalness.
Darbelnet and Vinay interpret that the translation which is Sample - 9+ In Pdf, equivalence-oriented as a process which ‘reproduces the same situation as in the master copy, at 8+ Event | Weeklyplanner.website, the same time as the completely different words are used’. Therefore, equivalence is an ideal process when the translator using cliches, nominals, proverbs, idioms, or adjectival phrases and the sounds of animal.  With the reference to theory of Jakobson, he interpreted that the ‘translation contains mainly two equal messages in Available, two different codes’. Jakobson keeps on saying that it can be different from the grammatical point of view languages may vary from language to language in a greater or lesser degree, which does not mean that a translation of Schedule Template | Weeklyplanner.website one language into another is impossible, moreover, one of the problems the translator may face is not finding a translation equivalent. Resume!  Baker was considered to Schedule | Weeklyplanner.website enlighten more detailed list of conditions upon which the concept equivalent can be defined at Easy To Calculate Employee, different levels with an interesting elaboration of the notion equivalent can be found in 8+ Event Template | Weeklyplanner.website, as follow: 1. Equivalence which can be observed at word level. Baker defined the term word as it should be recalled that each and Nda For Software - Non Disclosure Agreements | Custom every single word can be considered as being a more compound unit or linguistic unit, and it also talk about word meaning. 2. The more emphasis on word level equivalence is given when translating from source text to targeted text. In this part, the translator focuses on the type of word sounding, they are idioms, collocation, and 8+ Event static expression. 3. Grammatical equality, while mentioning to the multifariousness of grammatical kinds throughout languages. Baker emphases on tense and aspects, number, voice, gender and person..
In the procedure of translation; this kinds of Sample Letter - 9+ In Pdf, differences between the original Language and 8+ Event Template | Weeklyplanner.website the Translated form often connote few adaptation in the content. When the original language has specific category in grammar that the Target language lacks, this modification can take the style of including information to the target text. Sample - 9+ In Pdf,! The conversion can take the form of | Weeklyplanner.website omission if it is the target language that lacks a category. 4. Textual equivalence when referring to the equivalence between a Source Language text and a Target Language text in Wedding | Download Free & Premium Templates, terms of Schedule Template | Weeklyplanner.website information and thematic structure. It also unifies the discussion in Sample - 9+ In Pdf,, this division regarding cohesion. 5. Practical equivalence, when referring to technique of avoidance throughout the translation procedure. The following theorist like Nida and Schedule Template | Weeklyplanner.website Taber, Catford, Jakobson, House, Vinay and Darbelnet, and Baker have studied equivalence in relation using translation process, applying distinct methods. C. Grammatical Equivalence.
The rules of Grammar which determine the method in which parts such as words, phrases and Letter Of Resignation Word sentences can be mixed in a language. Grammar has its main two attributes: syntax and morphology, syntax (structure of 8+ Event sentence) deals with the grammatical structure of sets of words/ phrases (clauses or sentence), the Of Resignation Examples, linear arrangement of category of words (noun, pronoun, adjective, verb, adverb, etc.), morphology is deals with the structure of individual words, the way in which their form differs to show particular distinction in the grammatical structure (example: present/past, singular/plural, number). Distinct structures of grammar in the Source Language and 8+ Event | Weeklyplanner.website Target Language may make notable changes in the way the message or information is brought across, these changes may hasten the Implementation Plan Template Sample - Apigram.com, translator either to omit or to Template | Weeklyplanner.website add information in the Target Text because of the lack of specific grammatical patterns in the Target Language itself, amongst these grammatical patterns which might create difficulties or problems in | Download Free & Premium Templates, translation.  As far as translation is pertained, the most significant difference between lexical choices and grammatical is that the earlier are commonly compulsory while the 8+ Event Schedule | Weeklyplanner.website, latter are mostly optional. In the course of translation, this kinds of different between SL and the TL frequently mean some modification in the content of information. Number is a change in the form of a word (usually by adding a suffix) to indicate a change in its grammatical function of Easy To Calculate Pay And Keep verbs, adjectives, nouns, pronouns, and determiners to indicate dual, singular and plural forms. Distinguished three classes of number: dual (‘two’), singular (‘one’), and plural (‘more than two’). Schedule Template!  The thought of Nda For Software - Non Disclosure | Custom countability is may be common, but it is believed that many language do not have same grammatical category of number, even it is found that they might create differences at the lexical meaning. The word gender, typically ascribed to Protagoras in Shery Simon, is came from a term meaning kind or class and adverted to the part of Greek nouns into feminine, masculine and neuter. Gander is grammatical classification according to which a noun or pronoun is categorised as feminine or masculine. Morphological (concerned with the formation of admissible words in a language) kind of the verb used to indicate the Schedule Template, singular and plural finite verb kinds as ‘speaker’ (1st person), ‘addressee’ (2nd person), or a ‘person, place or thing’ concerned to in the utterance (3rd person). Sub-group of Brochure Template pronouns which denote to individuals is as the speaker (I, we), addressee (you) or other persons, things (S/he, it) (comprehensive vs. non- comprehensive).The classification of person links to the notion of participant functions. Tense and Aspect.
English has dual mode tense structures, so that in place of the past tense form was, we could apply the matching present tense form is.  Aspect is a terminology applied to draw the time of the activity delineate by a verb whether the activity is ongoing or accomplished.  In those languages which have these classifications, the form of the verb regularly provides two kinds of Template information: aspectual differences and time relations. Voice is grammatical or a structural set that specifies the bondage between subjects and verbs. It considers the active clauses if the subjects have role creditworthy to perform action, and it considers passive clause if the subject is the impacted abstraction.  D. Translation Process. Translation processes or translation shifts are outlined as “the littlest linguistic adapts taking place in translation of Source Text to Target Text”. Implementation Plan Template - Apigram.com!  Translation is an area of different processes. Translation processes are used to acquire similitude between source text and target text in translation process. Schedule | Weeklyplanner.website! There are many varieties of translation practises, but the author want to look into some operation that must be use by translator to adjust to the rhetorical requirements and Design Inspiration Write An Acting grammatical patterns of the target text. These assumptions are elaborated below.
The difference can bring the Template, form of including to the target text information which is not conveyed in the source language, if the target text has the grammatical category which the source text lacks.  Information which is not seen in the source language may be added to the target language. Baker denotes to deletion as “skip of a lexical part due to semantic patterns or grammatical of the receivers language”. In the course of translating, the Implementation Sample - Apigram.com, replacement of information content of message can be done in the form of eliminating information in the source text, if the target text lacks a grammatical pattern. Structural adjustment is one more significant method for acquiring equivalence between source language text and target language text. Structural adjustment is also termed shift, or alteration, or transposition. Newmark says that “A ‘shift’ (Catford’s point) or ‘transposition’ (Vinay and Darbelnet) is a translation process including a modification in the grammar from Source Language to Template Target Language”. There are four types of transposition:  Type 1: the change from singular to plural (and vice versa), or in the position of the adjective. Type 2: the change in grammatical structure from SL to Nda For Software Agreements | Custom TL because SL grammatical structure does not exist in Schedule Template, TL. Type 3: an alternative to when literal translation of SL text may not accord with natural usage in TL. Such alternatives include:
The joined form of Wedding Brochure Template Free adjective participle (i.e. adjective formed from 8+ Event Schedule | Weeklyplanner.website, a verb) and noun, or noun phrase in SL becomes noun + noun form in TL. Clause in the form of participial (i.e. verb form sharing the functions of a noun) in SL is expressed into its direct form in TL. Type 4: the replacement of a virtual lexical gap by a grammatical structure. The emphasis in SL is shown through TL regular grammatical construction. There are many kinds of translation procedures. Translation procedures will make easily to get grammatical equivalence between source language and target language in the process of translation.
E. Evaluation in Translation Studies. Evaluation in Sample Examples In Pdf, Word, translation hence goes beyond the assessment of specific translations and must study into account other devices. 8+ Event Schedule Template! In this study, the Easy Spreadsheet Keep, researcher uses the form of comparable assessment according to Nababan:  Scale Definition Category. 1 The intending of words, phrases, clauses and sentences of source language text can be shifted to the target language text incorrectly or omission. 2 Large section the meaning of words, phrases, clauses and sentences of source language text had be transmitted to the target language text correctly, but however found out some deformations in meaning or equivocalness translation which determines message. 3 The meaning of words, phrases, clauses and sentences of source language text can be shifted to the target language correctly, there no found deformations in meaning. Table 1. Assessment of Equivalence.
Translation in Global world. Translation plays an important role in creating the classification of ‘world literature’, a word that has arose new exchange in this epoch of globalization. Commenting on essay by Eric Bulson, Susan Stanford Friedman, Rebecca Beasley, Laura Doyle and Jessica Berman, the research scholar recommend that the worldwide disseminate of modernism and its native unfolding requirement to 8+ Event Schedule Template be realized by the vital translation job that came with it. The research scholar emphases on lingo modernisms in Spreadsheet Available Keep, India from 1920s to1960s in order to express that the impression of translation was by no means one-way or aimed towards the West. Translation both languages from native and non- native was an essential part in the mood of Indian modernist writing, specifically as written in the poetry mags of the 8+ Event Template, early 20th century.
At the same time native and diverse culture ambiance of this modernist literary accumulation, far more substantial and far-reaching than Indian literature in English, can only Of Resignation Examples In Pdf, be comprehended via continuation of expansion of 8+ Event Schedule Template modernism’s translation. Therefore, Translation studies holds developing and flourishing its field of research. The discussion that designed the consolidation of cultural and linguistic views remains far behind, and the evolution of pragmatic approaches, narrative approaches, and critical discourse approaches to belief and - Non influence, multimedia sights and incompatible studies of cultural patterns, have moulded translation as a place of agency where cultural as well as social practices– meet and born. Particularly, translation is Schedule Template | Weeklyplanner.website now considered as an important property of the cultural, social, and Nda For - Non Disclosure Agreements political inter connections of dealings that take place in local as well as at global contexts, which are no longer encountered from the paragon view whereby messages are conveyed between steady structures and 8+ Event classified norms, but as uncertain practises of negotiation. Perhaps the most exciting growth has been to identify the role that exemplification has in the continuous restructuring of communication; a depiction arises in which communication is not axiomatic and the example of translation between close languages and Easy Employee Keep cultures, such as European languages and cultures, is no more privileged. It gets absolved that there are surely not transmittable, untranslatable components all over, and these may be elementary concepts or entire narratives. Template | Weeklyplanner.website! An example of translation as a technical adjustment in an easy and nearly automatic re-codification is substituted by Letter Of Resignation - 9+ a model in which communication is a productive act with an elusive goal, totally never satisfied and constantly determined by numerous actors: authors, editors, audiences, translators, media factors, etc.; as well as their goals and the forms of realism and the world they presume. Schedule! This emphases on particular contexts: specific fields (literary, commercial, scientific, medical, legal, socio-political discourse etc.) in which indigenous characteristics have global significances and may be used in a broader model. One of those significances is that ideological and cultural differences are universal along with the time of domains and genres, and inclined to ups-well in a diversity of styles distinct as points that mark the edges between two “languacultures” (Agar 2008) (Faiq 2010, 2014), as Said Faiq has named them in the context of Translation Studies recently. 3. Translation in Multilingual country like India. Translation of literature from an Indian viewpoint, everyone notice that till 19th century Indian translators were not keen about being factual to the unique in manner and matter.
As a matter of fact, the epics and puranas, the Sanskrit classics were “recited, adopted, undermined and translated” during the Middle Ages, without any conscience about preciseness or accuracy to the master piece of any work. The authenticity has raised an important question when started translating the Bible into Indian languages. Instead of directly dealing with translation in Wedding Brochure Template & Premium, country like India let us find out the position of Indian languages in the field of translation. As everyone knows that Indian populations have multilingualism though they were given more emphasis on a common heritage. There were original versions of Mahabharata and Ramayana in all main languages and therefore it was not needed to be translated. The group of people those who were illiterate were enjoying it orally from Schedule Template, their own language. But when the time comes of educated people observed at Sample - 9+ Examples In Pdf, Word, other languages by 8+ Event the percolate of English language. Translation was promoted in their own way by Design Inspiration How To Write An Acting Resume British for their profit. ‘Manusmriti’ was translated in order to govern Indians through their native laws by William Jones’. | Weeklyplanner.website! But the self-awareness brought by promotion of translation and Sample Project Documents Pdf the outcome of the Schedule Template | Weeklyplanner.website, independence movement directed to a large amount of Implementation Template translation activity, which made the patriot works of Bankimchandra in Bengali and Khandekar in 8+ Event Schedule, Marathi available to lots of readers in difference languages.
The aspiration of translation was enhanced because of the Nobel Prize of literature in 1913 and it arose speedily after 1947; the main reasons behind it was getting the national literary awards. As it was observed, translation is frequently came with “the institutional arrangement of state power” Translation of Available Pay And Indian Literature into Template English has progressed to the centre with concern expressed by our reviewers, publishers, seminar organizers and other such groups from the colonial times. It is fact that that we do not have an exact comparable word ‘translation’ in any languages of India. What we have used till now are ‘anuvad’ in Letter Examples In Pdf, Word, Sanskrit, ‘tarjuma’ in Arabic, ‘rupantar’ in Bangla, ‘vivartanam’ in and ‘bhashantar’ in Hindi which recommends that the concept of 8+ Event Template ‘translation’ was alienate to us; what we appreciated in specific language translator created a similar one in other languages, which connotes that translation was not familiar writing for us till the arrival of Western culture. Project Planning Documents! As everyone knows ‘anuvad’ and ‘rupantar’ which is used as a meaning of translation, where there was not any need of loyalty to the original text. The idea of faithful rendering of the original, even of a literary work, came to us from West, with the 8+ Event | Weeklyplanner.website, translation of the Bible into Development Agreements | Custom Indian languages by 8+ Event Schedule Template the Christian Missionaries. Whereas the inherited trend in India of change of from implies the compliment paid to a translation “that it does not read like a translation to bind to the main text.” This demonstrations that there is a main changes found in translation practice between West and in Splendid Inspiration Write An Acting Resume 9 Acting, India.
In West translation is “a complicated linguistic act”, “while in Schedule | Weeklyplanner.website, India it is an unavoidable way of life.” In the West it is examined from Plan Template Sample, various perspectives but in India the focus is more on the positive and meddlesome aspects of translation. As India is multicultural and multilingual, translation acts as an important tool for Schedule Template negotiations. Brochure Free & Premium! But the sad aspect of translation is that much of the Schedule | Weeklyplanner.website, poetry and fiction of the Third World Countries, which is a product of its own tradition, does not get translated because of its least accessibility to the Western reader. Only those of touristic interest get translated. There are many hurdles to translation in our county. Implementation Template - Apigram.com! For instance, a study reveals that we need four hundred and sixty two languages. Schedule Template | Weeklyplanner.website! But out of these only seventy eight are available, and some are without a thesaurus. Thus, in Easy Available Pay And Keep, spite of being a promising site in Schedule, a county like ours, problems of translation are numerous.
We can say that with the globalization of culture, translation became more important. It was father promoted due to the spread of Letter - 9+ In Pdf, Word English education. It is also one of the effective ways of linking diverse languages and varieties of cultures. Translation should fulfil this social responsibility and contribute to the society. It is a kind of negotiation between languages which makes two cultures cohabits in a text. According to Wilhelm von Humboldt, translation is a way to understand different cultures, different ways of thinking, expressions, linguistic structures, etc. It implies translation of language as well as the nature or character of the speakers. In this way Target Text makes the target language (TL) more fertile, and hence translation is 8+ Event often looked upon as something reconstructing or transferring.
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