Search

Background When cancer treatments have similar oncologic outcomes, the number of days with in-person healthcare contact (“”contact days’’) can help contextualize expected time use with each treatment. We assessed contact days in a completed randomized clinical trial. Patients and Methods We conducted a secondary analysis of the CCTG LY.12 RCT that evaluated 2-3 cycles of gemcitabine, dexamethasone, and cisplatin (GDP) vs. dexamethasone, cytarabine, and cisplatin (DHAP) in 619 patients with relapsed/refractory lymphoma prior to stem cell transplant. Primary analyses reported similar response rates and survival. We calculated patient-level “contact days” by analyzing trial forms. The study period was from assignment to progression or transplant. Days without healthcare contact were considered “home days’’. We compared measures of contact days across arms. Results The study period was longer in the GDP arm (median 50, vs. 47 days, P = .007). Contact days were comparable in both arms (median 18 vs 19, P = 0.79), but home days were higher in the GDP arm (median 33 vs 28, P < .001). The proportion of contact days was lower in the GDP arm (34%, vs. 38%, P = .009). The GDP arm experienced more contact days related to planned outpatient chemotherapy (median, 10 vs. 8 days), but the DHAP arm experienced many more inpatient contact days (median, 11 vs. 0 days). Conclusions Measures of time use, such as contact days, can be extracted from RCTs. In LY.12, despite comparable oncologic outcomes, GDP was associated with fewer contact days. Such information can guide decision-making for patients with hematological cancers, who already face significant healthcare contact.

PURPOSE The time spent in pursuing treatments for advanced cancer can be substantial. We have previously proposed a pragmatic and patient-centered metric of these time costs—which we term time toxicity—as any day with physical health care system contact. This includes outpatient visits (eg, bloodwork, scans, etc), emergency department visits, and overnight stays in a health care facility. Herein, we sought to assess time toxicity in a completed randomized controlled trial (RCT). METHODS We conducted a secondary analysis of the Canadian Cancer Trials Group CO.17 RCT that evaluated weekly cetuximab infusions versus supportive care alone in 572 patients with advanced colorectal cancer. Initial results reported a 6-week improvement in median overall survival (OS) with cetuximab (6.1 v 4.6 months). Subsequent analyses reported that benefit was restricted to patients with K-ras wild-type tumors. We calculated patient-level time toxicity by analyzing trial forms. We considered days without health care contact as home days. We compared medians of time measures across arms and stratified results by K-ras status. RESULTS In the overall population, median time toxic days were higher in the cetuximab arm (28 v 10, P < .001) although median home days were not statistically different between arms (140 v 121, P = .09). In patients with K-ras–mutated tumors, cetuximab was associated with almost numerically equal home days (114 days v 112 days, P = .571) and higher time toxicity (23 days v 11 days, P < .001). In patients with K-ras wild-type tumors, cetuximab was associated with more home days (186 v 132, P < .001). CONCLUSION This proof-of-concept feasibility study demonstrates that measures of time toxicity can be extracted through secondary analyses of RCTs. In CO.17, despite an overall OS benefit with cetuximab, home days were statistically similar across arms. Such data can supplement traditional survival end points in RCTs. Further work should refine and validate the measure prospectively.

A novel ferrate(VI)/titanium dioxide/ultraviolet [Fe(VI)/TiO2/UV] system was successfully established for the photocatalytic oxidation of dimethyl phthalate (DMP). This system demonstrated a higher removal efficiency of DMP (95.2%) than the conventional TiO2/UV and Fe(VI) alone systems (51.8% and 23.5%, respectively) and produced obvious synergistic effects. Response surface methodology (RSM), based on a three level, three independent variables design, was conducted through Design Expert 8.0.6 program, and a second-order polynomial model (R2 = 0.998) was developed to quantitatively describe the photocatalysis of TiO2 combined with Fe(VI) oxidation under ultraviolet irradiation. The fresh TiO2 and photochemical reacted Fe(VI)/TiO2 were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and element dispersive spectrum (EDS), which indicated that Fe(VI) was imprinted into the TiO2, and the surface adsorbed Fe-O-(organic) materials inhibited DMP degradation. This photocatalytic oxidant showed high activity and stability after nine cycles without loss of its effectiveness (counting from the second cycle). The intermediates/products of DMP were analyzed by gas chromatography-mass spectrometry. The proposed pathway for DMP degradation involved one electron transfer of hydroxyl radical and breaking of the ester bond and benzene ring. The mineralization efficiencies of DMP in actual industrial wastewater and simulated water were 87.1% and 95.2%, respectively, suggesting practical field applications. A ecotoxicity test (17.3% inhibition on bioluminescence) in treating actual industrial wastewater containing DMP implied that the proposed Fe(VI)/TiO2/UV had a potential for industrial water treatment.

Studies on targeting cancer stem cells (CSCs) have not yielded satisfactory results regarding solid tumor treatments; one of the reasons for this is the difficulty associated with the identification of a relatively specific antigen in solid tumors. CD14, which is mainly expressed in certain immune cells, is associated with tumor recurrence, growth, metastasis and resistance to treatment, which is in conformity with the characteristics of CSCs. It was thus hypothesized that esophageal CSCs (ECSCs) express CD14. In the present study, paraffin‑embedded sections of human esophageal carcinoma were used to determine the co‑expression of CD14 and the ECSC marker aldehyde dehydrogenase‑1 (ALDH1) using immunofluorescence. CD14

There is a rising concern that air pollution plays an important role in the COVID-19 pandemic. However, the results were not consistent on the association between air pollution and the spread of COVID-19. In the study, air pollution data and the confirmed cases of COVID-19 were both gathered from five severe cities across three countries in South America. Daily real-time population regeneration (Rt) was calculated to assess the spread of COVID-19. Two frequently used models, generalized additive models (GAM) and multiple linear regression, were both used to explore the impact of environmental pollutants on the epidemic. Wide ranges of all six air pollutants were detected across the five cities. Spearman’s correlation analysis confirmed the positive correlation within six pollutants. Rt value showed a gradual decline in all the five cities. Further analysis showed that the association between air pollution and COVID-19 varied across five cities. According to our research results, even for the same region, varied models gave inconsistent results. For example, in Sao Paulo, both models show SO2 and O3 are significant independent variables, however, the GAM model shows that PM10 has a nonlinear negative correlation with Rt, while PM10 has no significant correlation in the multiple linear model. Moreover, in the case of multiple regions, currently used models should be selected according to local conditions. Our results indicate that there is a significant relationship between air pollution and COVID-19 infection, which will help states, health practitioners, and policy makers in combating the COVID-19 pandemic in South America. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-021-15508-8.

Introduction: Analyses of circulating tumor DNA (ctDNA) have shown promise in capturing tumor burden dynamics during immune checkpoint blockade (ICB), with the potential to allow patients with primary resistance to be rapidly identified and redirected to alternative therapies. Methods: BR.36 is an international multicenter, open label, biomarker-directed, phase II trial of molecular response-adaptive immuno-chemotherapy for patients with treatment-naïve non-small cell lung cancer-NSCLC (NCT04093167). The trial consists of two stages; stage 1 was a single-arm study to validate the ctDNA approach, with stage 2 focusing on ctDNA guided treatment selection. Key eligibility criteria included EGFR and ALK mutation negative, ICB and chemotherapy-naïve metastatic NSCLC with PD-L1 expression ≥1%. Primary objectives were to ascertain ctDNA molecular response, determine its timing and concordance with radiologic RECIST/iRECIST response. Secondary objectives included the evaluation of time to ctDNA molecular response and its correlation with progression-free (PFS) and overall survival (OS). Liquid biopsy analyses utilized a validated tumor-agnostic white blood cell (WBC) DNA-informed 33-gene panel approach. Ultra-sensitive error-correction ctDNA next-generation sequencing (NGS) was performed at baseline/cycle 1 (C1D1), cycle 2 (C2D1) and cycle 3 (C3D1) of pembrolizumab (200mg IV q3 weeks). The maximum variant allele fraction (maxVAF) of tumor-derived variants was tracked from the pre-treatment to on-therapy timepoints. Results: Activated October 17, 2019, stage 1 completed accrual of 50 patients on April 5, 2022; data lock date was September 20, 2022. Most patients were ever-smokers (98%), had no prior systemic therapy (92%), stage IV NSCLC (98%), adenocarcinoma (76%) with PD-L1 tumor proportion score of ≥ 50% (96%); cohort consisted of 82% white, 52% female, 56% age>65 and 76% ECOG PS 1 participants. Median follow-up was 13.5 months (range 2.5-23.0). Best overall response rate (ORR) by RECIST was 32% with a median duration of 10.1 months. Matched WBC DNA analyses allowed for effective removal of germline and clonal hematopoiesis variants, followed by evaluation of ctDNA response. MaxVAF clearance signified molecular response (mR), while maxVAF persistence indicated molecular disease progression (mPD). Among 35 evaluable patients (77.8%), 15 were classified in the mR category, with an evaluable mR rate of 43% (90% CI: 0.29-0.58). The median time to molecular response was 2.1 months (90% CI: 1.5-2.6). The sensitivity of ctDNA molecular response for RECIST and iRECIST response was 82% (90% CI: 52%-97%) and 83% (90% CI: 56%-97%), with a specificity of 75% (90% CI: 56.5%-88.5%) and 78% (90% CI: 60%-91%) respectively. Patients with mR attained longer PFS (5.03 vs 2.6 months,) and OS (not reached vs 7.23 months); ctDNA response also provided prognostic information for patients with RECIST stable disease. Conclusions: ctDNA molecular responses were concordant with radiologic response assessments, but importantly better predicted PFS and OS for patients with stable disease or better. These findings are now incorporated into the interventional second stage of the trial. Citation Format: Valsamo K. Anagnostou, Cheryl Ho, Garth Nicholas, Rosalyn Anne Juergens, Adrian Sacher, Andrea Fung, Paul Wheatley-Price, Scott Laurie, Benjamin Levy, Julie Brahmer, Archana Balan, Noushin Niknafs, Egor Avrutin, Liting Zhu, Mark Sausen, Penelope Bradbury, Jill O'Donnell-Tormey, Pierre-Olivier Gaudreau, Keyue Ding, Janet Dancey. A ctDNA-directed, multi-center phase II study of molecular response adaptive immuno-chemotherapy in patients with non-small cell lung cancer: Analysis of Stage 1 of CCTG BR.36 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT212.

Extracellular vesicles (EVs) are newly recognized as important vectors for carrying and spreading antibiotic resistance genes (ARGs). However, the ARGs harbored by EVs in ambient environments and the transfer potential are still unclear. In this study, the prevalence of ARGs and mobile genetic elements (MGEs) in EVs and their microbial origins were studied in indoor dust from restaurants, kindergarten, dormitories, and vehicles. The amount of EVs ranged from 3.40 × 10

Background The purpose of this retrospective biomarker study of the Canadian Cancer Trials Group (CCTG) MA.31 randomized phase 3 trial (lapatinib vs trastuzumab) of HER2-positive metastatic breast cancer (MBC) was to evaluate the prognostic and predictive biomarker utility of pretreatment serum programmed death ligand 1 (PD-L1) levels. Methods CCTG MA.31 accrued 652 HER2-positive patients; 387 had serum available (185 in the trastuzumab arm and 202 in the lapatinib arm). The Ella immunoassay platform (ProteinSimple, San Jose, California) was used to quantitate serum PD-L1 levels. Stepwise forward Cox multivariable analyses were performed for progression-free survival and overall survival (OS). Results In the whole trial population, continuous pretreatment serum PD-L1 levels were not associated with OS. However, within the trastuzumab arm, a higher continuous pretreatment serum PD-L1 level was significant for shorter OS (hazard ratio [HR], 3.85; P = .04), but within the lapatinib arm, pretreatment serum PD-L1 was not associated with OS (P = .37). In the whole trial, in a multivariable analysis for OS, serum PD-L1 (median cut point) remained a significant independent covariate (HR, 2.38; P = .001). There was a significant interaction between treatment arm and continuous serum PD-L1 (bootstrap method; P = .0025): at or above 214.2 pg/mL (the 89th percentile), serum PD-L1 was associated with significantly shorter OS with trastuzumab treatment versus lapatinib treatment. Conclusions In the CCTG MA.31 trial, serum PD-L1 was a significant predictive factor: a higher pretreatment serum PD-L1 level was associated with shorter OS with trastuzumab treatment but with longer OS with lapatinib treatment. Immune evasion may decrease the effectiveness of trastuzumab therapy. Further evaluation of elevated serum PD-L1 in advanced breast cancer is warranted to identify patients with HER2-positive MBC who may benefit from novel immune-targeted therapies in addition to trastuzumab.

The paper focuses on the socio-economic factors of municipal solid waste generation (MSWG) in China. China achieves a rapid economic development since the economic reforms adopted in 1978. The study shows that only 33percent of population lived in urban areas in 1985 that increased to 54 percent in 2014. Consumption expenditure rate increases to 3.96 percent and solid waste generation rose about 2.96 percent annually from 1990 to 2014. A huge amount of solid waste in urban areas causes serious environmental woes and human health hazards that are hindrance to sustainable urban development. The study aims at finding out the associational effects of purchasing power parity (PPP) and consumption expenditure rise (CER) on the solid waste production. The paper shows the negative association of purchasing power parity (PPP) and consumption expenditure rise with solid waste production and their relationship is significant at 5% level. In addition, rapid urbanization is positively correlated to consumption expenditure rise and it is significant at 5%level as well. I prepare the dataset using the extracted annual and national records of National Bureau of Statistics of China and World Data Indicator (WDI) from 2000 to 2015. I analyzed the data applying Correlation Matrix and Multiple Linear Regression Analysis. The findings will facilitate to formulate efficient solid waste management to sustainable urbanity.

The ecological risks and health hazards of heavy metals pollution in Taihu Lake have received widespread concern. This study has developed a nationwide dataset on pollutant loads in species, and the dataset records 55,297 data from 310 articles, covering 778 species and 537 pollutants. In this paper, we extract and systematically integrate data on heavy metals concentrations in Taihu fish from the dataset. The Pi (single pollution index) and MPI (metal pollution index) models were used to assess the level of contamination in fish and the THQ (target hazard quotient) and ILCR (incremental lifetime cancer risk) models were used to assess the health hazards of fish consumption. The contamination levels varied in a feeding habit and living habit dependent manner. The risk of non-cancer health is the highest in omnivorous fish, then in carnivorous fish and herbivorous fish. ILCR model predicted that the values of As and Cd in omnivorous fish for children exceeded the risk threshold limits set by the EPA, and the ILCR values of As in omnivorous fish and Cd in carnivorous fish for adults also exceeded the risk threshold limits. In all, this study provided a comprehensive understanding of the risk of heavy metals in Taihu.

248 Background: Most individual treatments for advanced cancer are associated with modest survival benefits. The time spent in pursuing these treatments can be substantial. We have previously developed a pragmatic and patient-centered metric of these time costs, which we term ‘’time toxicity’’, as any day with physical healthcare system contact. This includes outpatient visits (e.g., for bloodwork, scans, infusions, urgent care), emergency room visits, and overnight stays in a healthcare facility. Herein we sought to assess time toxicity in a completed RCT. Methods: We conducted a secondary analysis of the Canadian Cancer Trials Group CO.17 RCT that evaluated weekly cetuximab infusions vs supportive care alone in 572 patients with advanced colorectal cancer. CO.17 recruited participants in Canada, Australia and New Zealand. Initial results reported a 6-week improvement in median overall survival (OS) with cetuximab (6.1 vs 4.6 months, p = 0.005). Subsequent analyses reported that OS benefit was restricted to and significantly more in patients with K-ras wild-type tumors. We calculated patient-level time toxicity by analyzing treatment, follow-up, and resource utilization forms. We considered a day without physical healthcare contact as a ‘’home day’’. Thus, for a patient, OS was time toxic days + home days. We compared medians of time measures across arms, and stratified results by K-ras status. Results: In the overall population, median time toxic days were higher in the cetuximab arm (28, vs 10, p < 0.001), although median home days were not statistically different (140, vs 121, p = 0.09). The proportion of time toxic days (time toxic days/OS) were significantly more with cetuximab (18%, vs 6%, p < 0.001). Of the 28 time toxic days in the overall cetuximab arm, 14 (50%) were protocol-related (e.g., scheduled infusions etc). Stratified results are in the table. Conclusions: Time toxicity can be extracted through secondary analyses of RCTs. In CO.17, despite an overall OS-benefit with cetuximab, home days were statistically similar across arms. In the K-ras-mutated group, cetuximab was associated with numerically similar OS but more time toxic days. In the K-ras-wild type group, cetuximab was associated with higher home days. Thus, time toxicity data need not always be sobering. Time toxicity measures can supplement traditional survival endpoints in RCTs to guide patient-oncologist decision-making. Cooperative group RCTs are well positioned for such analyses. Clinical trial information: NCT00079066. [Table: see text]

A novel ferrate (VI)/titanium dioxide/ultraviolet [Fe(VI)/TiO2/UV] system was successfully established for the photocatalytic oxidation of dimethyl phthalate (DMP). This system demonstrated a higher removel efficiency of DMP (95.2%) than the conventional TiO2/UV and Fe(VI) alone systems (51.8% and 23.5%, respectively), and produced obvious synergistic effects. Response surface methodology (RSM), based on a three level, three independent variables design, was conducted through Design Expert 8.0.6 program, and a second-order polynomial model (R2 = 0.998) was developed to quantitatively describe the photocatalysis of TiO2 combined with Fe(VI) oxidation under ultraviolet irradiation. The fresh TiO2 and photochemical reacted Fe(VI)/TiO2 were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and element dispersive spectrum (EDS), which indicated that Fe(VI) was imprinted into the TiO2, and the surface adsorbed Fe-O-(organic) materials inhibited DMP degradation. This photocatalytic oxidant showed high activity and stability after nine cycles without loss of its effectiveness (counting from the second cycle). The intermediates/products of DMP were analyzed by gas chromatography–mass spectrometry. The proposed pathway for DMP degradation involved one electron transfer of hydroxyl radical and breaking of the ester bond and benzene ring. The mineralization efficiencies of DMP in actual industrial wastewater and simulated water were 87.1% and 95.2%, respectively, suggesting practical field applications. A ecotoxicity test (17.3% inhibition on bioluminescence) in treating actual industial wastewater containing DMP implied that the proposed Fe(VI)/TiO2/UV has a potential for industrial water treatment.

Background: In the CCTG (Canadian Clinical Trials Group) MA.31 randomized phase 3 trial, the trastuzumab-taxane combination led to longer PFS than lapatinib-taxane in HER2-positive metastatic breast cancer (MBC). We previously reported the prognostic utility of pretreatment serum PD-L1 in the trastuzumab arm of MA.31 (ASCO 2018, #1031), and here we evaluate serum PD-L1 in the lapatinib arm, and in the whole trial. Higher serum PD-L1 has been reported to be associated with reduced response to treatment with the immune checkpoint inhibitors in melanoma and lung cancer. Methods: MA.31 accrued 652 centrally and/or locally-identified HER2-positivepatients; 186 in the trastuzumab arm, and 202 in the lapatinib armhad pretreatment serum available. TheELLA immunoassay platform (ProteinSimple, San Jose, CA) was used to quantitate serum PD-L1. Step-wise forward Cox multivariate analysis was used for PFS and OS, and testing for treatment-biomarker interaction was based on the local partial-likelihood method (Liu Y, Jiang W, and Chen BE, Statistics in Medicine 34, 3516-3530, 2015). Results: In the total study population, pretreatment serum PD-L1 concentration had a median of 86.2 pg/ml, and 25% and 75% interquartiles of 64.1 and 134.3 pg/ml, respectively. In univariate analysis in the whole trial, and within both treatment arms, serum PD-L1 was not a significant biomarker for PFS. For OS, higher serum PD-L1 (as a continuous variable) was significant for shorter OS within the trastuzumab arm (HR=3.84, p=0.04), but was not associated with OS in the lapatinib arm (p=0.37). In the whole trial, in multivariate analysis for OS [15 covariates included: age, race, ECOG status, anthracyclines, other chemo, endocrine, radio, other prior adjuvant therapy, disease status, ER status, PR status, Ki67 (log transformed), CK5, EGFR, treatment arm, and serum PD-L1 (with median cut point)], serum PD-L1 remained a significant independent covariate (HR= 2.27, p= 0.001 (Table).There was significant interaction between treatment arm and continuous serum PD-L1 (Bootstrap method, p=0.0025); above 214.2 pg/ml serum PD-L1 (89% percentile), higher pretreatment serum PD-L1 was associated with a shorter OS to trastuzumab treatment, but longer OS to lapatinib treatment. Conclusions: In the CCTG MA.31 trial, serum PD-L1 was a significant predictive factor: higher pretreatment serum PD-L1 was associated with a shorter OS to trastuzumab treatment, but longer OS to lapatinib treatment. Immune evasion may decrease the effectiveness of trastuzumab therapy. Further evaluation of elevated serum PD-L1 in the advanced breast cancer setting is warranted to identify HER2-positive MBC patients who may benefit from novel immune-targeted therapies in addition to trastuzumab. Multivariate Analysis (whole trial): Significant Independent CovariatesCovariateP-ValueHRLower 95% CIHigher 95% CISerum PD-L1 (pretreatment) (>median vs Citation Format: Moku PR, Shepherd LE, Ali SM, Leitzel K, Parulekar WE, Zhu L, Virk S, Nomikos D, Aparicio S, Gelmon KA, Drabick JJ, Cream L, Halstead SE, Umstead T, Mckeone D, Maddukuri A, Polimera HV, Ali A, Poulose J, Pancholy N, Spiegel H, Nagabhairu V, Chen BE, Lipton A. Higher serum PD-L1 predicts for increased overall survival to lapatinib vs trastuzumab in the phase 3 CCTG MA.31 trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD3-10.

There is a rising concern that air pollution plays an important role in the COVID-19 pandemic. However, the results weren’t consistent on the association between air pollution and the spread of COVID-19. In the study, air pollution data and the confirmed cases of COVID-19 were both gathered from five severe cities across three countries in South America. Daily real-time population regeneration (Rt) were calculated to assess the spread of COVID-19. Two frequently used model, generalized additive models (GAM) and multiple linear regression, were both used to explore the impact of environmental pollutants on the epidemic. Wide ranges of all the six air pollutants were detected across the five cities. Spearman's correlation analysis confirmed the positive correlation within six pollutants. Rt value showed a gradual decline in all the five cities. Further analysis showed that the association between air pollution and COVID-19 varied across five cities. Multiple linear regression and GAM did not give the same trend in a specific city. For example, in Sao Paulo, the GAM model shows that PM10 has a nonlinear negative correlation with Rt, while PM10 has no significant correlation in the multiple linear model. According to our research results, even for the same region, varied models gave inconsistent results. Moreover, in the case of multiple regions, current used models should be selected according to local conditions.

A novel ferrate(VI)/titanium dioxide/ultraviolet [Fe(VI)/TiO

Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus, causes lethal watery diarrhea to the piglets, which poses significant economic losses and public health concerns. The nsp10 protein of PEDV is essential regulatory subunits that are critical for virus replication. Since PEDV nsp10 is a crucial regulator of viral RNA synthesis, it is promising that nsp10 might become anti-virus drugs target or candidate for rapid diagnosis of PEDV infection. In this study, the PEDV nsp10 was inserted into pMAL-c2x-MBP / pET-28a vector, efficiently and stably expressed in E.coli system. Then the purified nsp10 protein was found to mediate potent antibody responses in immunized mice. The antibodies of immunized mice and PEDV infection swine strongly recognized purified nsp10 protein from cell lysates. Furthermore, cytokines test revealed that the expression of IL-2, IL-4, IL-10, TNF-α, IFN-γ were significantly higher than those in control group, indicated that purified nsp10 protein induce the cellular immune response mechanism in mice. Using modified seroneutralization test, we also demonstrated that sera from nsp10-immunized mice inhibited PEDV replication to some extent. These findings suggest that nsp10 has a high immunogenicity. This study may have implications for future development of PEDV detection or anti-virus drugs for swine.

In this paper, HFSS FEM-IE is employed for the design of 1-D transmitarray antenna with complicated feed array antenna and phase-correcting layers. Two new designs of the beam scanning and beam shaped 1-D transmitarray antennas are presented. The success of these designs is validated from the simulated results.

Pinus massoniana Lamb. is one of the most sensitive species to acid deposition among forest woody plants, but differences in acid resistance among pine families still exist. It is of great significance to study the differences in acid resistance of Masson pine families and to analyze the physiological regulation mechanism of their acid resistance. In this study, the 100-day-old seedlings of 16 Masson pine families were treated with the simulated acid rain (SAR) at different pH levels (5.6, 4.5, 3.5 and 2.5) for 100 days to investigate the plant morphology, chlorophyll content, and root physiological responses. Results showed that pine family No. 35 maintained the good morphology, high chlorophyll content and organic acids secretion, and low plasma membrane permeability exposed to SAR, while family No. 79 presented the opposite. SAR not only increased the root plasma membrane permeability, but also induced an exudation of organic acids from the pine roots, and the test parameters changed sharply when the SAR pH was lower than 4.5. The results indicated that Masson pine could resist to acidic environment (pH 4.5–5.6), and family No. 35 had the acid resistance while the family No. 79 was sensitive to acid stress. The acid resistance diversity of different pine families had close relation with the root physiological processes, including the root plasma membrane permeability and organic acids secretion. For the future research, the natural genetic variation of Masson pine in response to acid stress and its acid resistance mechanism should be further studied.

Based on the data collected from smart meters, electricity pricing models can be developed to balance power supply and demand in each time slot and obtain the optimal consumption loads and prices. However, in real life, users’ reserved consumption requirement loads sometimes deviate significantly from the optimal consumption loads obtained from models, which results in overloaded power systems or even power cuts. To address this issue, an Engineering Process Control monitoring strategy has been proposed in this paper to minimize the difference between the optimal and the users’ reserved consumption requirement loads. We proposed an exponential weighted moving average model to predict the load difference in future time slots, and also developed a novel quadratic function based demand response mechanism to adjust the power price for power providers. The demand response mechanism can be used to adjust the price in the future time slots when the predicted demand exceeds the upper or lower boundary. Simulation results indicate that the quadratic function adjustment strategy has excellent performance in a practical power market in Singapore. Compared with the linear function based adjustment method, the proposed quadratic function based adjustment method decreases the adjustment times and standard errors of residuals, and increases the social welfare and power suppliers’ profits under the same boundary conditions. In addition, the performance of the proposed strategy demonstrated its competency in peak-cutting and valley-filling and balancing energy provision with demands.

Hypothalamic Corticotropin-releasing factor (CRF) directly activates the hypothalamic pituitary adrenal axis (HPA axis) during the surgical trauma induced stress response. Electroacupuncture (EA) has been demonstrated to have stress relieving effects in breast surgery, colorectal surgery, prostatectomy and craniotomy. This study was aimed to investigate the hypothesis that EA could regulate hypothalamic CRF in surgical trauma rats. In experiment one, Sprague-Dawley (SD) male rats were divided into intact, model (10% partial hepatectomy), sham EA and EA group. Rats from the Sham EA and EA group were stimulated at ST36-Zusanli and SP6-Sanyiniiao acupoints twice, 24 hours before the surgery and immediately after the surgery. Expressions of hypothalamic CRF and CRFR, GABA receptors, glutamate decarboxylase (GAD), serum adrenocorticotropic hormone (ACTH) and Corticosterone (CORT) were observed at 2, 4, 8 and 24 h after the surgery by radioimmunoassay (RIA), western blot, real-time PCR and immunohistochemistry. In the experiment two, SD male rats were divided into the intact, model, model + vehicle, model + L-838,417 EA and EA + L838,417 group. It was found that hypothalamus CRF, serum ACTH and CORT levels were increased in model group compared with the intact group, and those in the EA group decreased in comparison with the model group. Compared with the model group, hypothalamus-aminobutyric acid (GABA) receptor Aα3 mRNA and protein expressions of the EA group raised strikingly. In conclusion, EA alleviated surgical stress response by improving the GABA synthesis in hypothalamus, thus enhancing GABA receptors’ inhibitory regulation of the HPA axis dysfunction in rats with acute surgical trauma.

Palliative radiotherapy (RT) is effective in patients with painful bone metastases. Genetic factors may identify subgroup of patients who responded to RT. To identify DNA biomarkers associated with response to palliative RT.Patients who received a single 8 Gy dose of RT for painful bone metastases were categorised into responders (n=36), non-responders (NR) (n=71). Saliva samples were sequenced to identify single-nucleotide variants (SNVs) in genes with known disease-causing variants from inflammation, radiation response, and DNA damage pathways. In univariate analysis, Cochran-Armitage trend tests were used to identify SNVs that associated with pain response (P0.005), and the Penalized LASSO method with minimum Bayesian Information Criterion was used to identify multi-SNVs that jointly predict pain response to RT. The corresponding estimated effect of the multi-SNVs were used to drive the prognostic score for each patient. Based on it, patients were divided into 3 equal size risk groups.Forty-one significant variants were identified in univariate analysis. Multivariable analysis selected 14 variants to generate prognostic scores, adjusting for gender and primary cancer site. Eighty-nine percent of patients in the high prognostic group responded to palliative radiation therapy (P=0.0001). Estimated effect sizes of the variants ranged from 0.108-2.551. The most statistically significant variant was a deletion at position 111992032 in the ataxin gene ATXN2 (P=0.0001). Five variants were non-synonymous, including AOAH rs7986 (P=0.0017), ZAN rs539445 (P=0.00078) and rs542137 (P=0.00078), RAG1 rs3740955 (P=0.0014), and GBGT1 rs75765336 (P=0.0026).SNVs involved in mechanisms including DNA repair, inflammation, cellular adhesion, and cell signalling have significant associations with radiation response. SNVs with predictive power may stratify patient populations according to likelihood of responding to treatment, therefore enabling more efficient identification of beneficial strategies for pain management and improved resource utilisation.

Background: Gender differences may contribute to variations in disease presentations and health outcomes. To explore the gender difference in pain and patient reported outcomes in cancer patients with bone metastases undergoing palliative radiotherapy on the National Cancer Institute of Canada (NCIC) SC.23 randomized trial. Methods: Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) bone metastases module (QLQ-BM22) and EORTC QOL Core-15-Palliative (QLQ-C15-PAL) before treatment and at days 10 and 42 after a single 8 Gy radiation treatment. Patient demographics, performance status, analgesic consumption, BM22 and C15 were compared between males and females using the 2-sample t-test for continuous variables or the Chi-squared test for categorical variables. Multiple linear regression models were used to check the difference between gender groups adjusting for the baseline demographics and primary disease sites. Results: There were 298 patients (170 male, 128 female) with median age of 69 years. The most common primary cancer sites were lung, prostate and breast. At baseline, there were no differences in BM22 and C15 scores, except a worse nausea and vomiting score (P=0.03) in females on the C15. In patients with moderate baseline worst pain scores (WPS), females reported worse scores in painful sites of BM22. At day 42, there was no significant difference in response to radiotherapy. Among the responders, females reported better improvement in emotional aspect. Conclusions: In cancer patients with bone metastases undergoing palliative radiotherapy, the majority of symptom presentations, patient reported outcomes, and response to radiation was not significantly different between genders. Trial registration: NCT01248585.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Although 5-year survival rates in the first-line setting range from 60% to 70%, up to 50% of patients become refractory to or relapse after treatment. Published analyses of large-scale outcome data from patients with refractory DLBCL are limited. SCHOLAR-1, an international, multicohort retrospective non-Hodgkin lymphoma research study, retrospectively evaluated outcomes in patients with refractory DLBCL which, for this study, was defined as progressive disease or stable disease as best response at any point during chemotherapy (>4 cycles of first-line or 2 cycles of later-line therapy) or relapsed at ≤12 months from autologous stem cell transplantation. SCHOLAR-1 pooled data from 2 phase 3 clinical trials (Lymphoma Academic Research Organization-CORAL and Canadian Cancer Trials Group LY.12) and 2 observational cohorts (MD Anderson Cancer Center and University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence). Response rates and overall survival were estimated from the time of initiation of salvage therapy for refractory disease. Among 861 patients, 636 were included on the basis of refractory disease inclusion criteria. For patients with refractory DLBCL, the objective response rate was 26% (complete response rate, 7%) to the next line of therapy, and the median overall survival was 6.3 months. Twenty percent of patients were alive at 2 years. Outcomes were consistently poor across patient subgroups and study cohorts. SCHOLAR-1 is the largest patient-level pooled retrospective analysis to characterize response rates and survival for a population of patients with refractory DLBCL.

To explore the age difference in response and patient-reported outcomes in patients with cancer having bone metastases undergoing palliative radiotherapy.Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life (QOL) Bone Metastases module (QLQ-BM22), EORTC QOL Core-15-Palliative (QLQ-C15-PAL), and Dexamethasone Symptom Questionnaire (DSQ) before a single 8-Gy radiation treatment, on days 10 and 42 after treatment. Patient demographics, performance status, analgesic consumption, BM22, C15, and DSQ were compared with multivariant analysis between patients under 75 years and 75 years and older. Multiple linear regression models were used to assess the differences between age-groups, adjusting for baseline demographics and primary disease sites.There were 298 patients (170 male) with 209 (70%) less than 75 years of age. Most common primary cancer sites include lung, prostate, and breast. At baseline, younger patients had better performance status, consumed more analgesic, and reported worse scores in nausea, insomnia, and functional interference, while older patients more commonly had prostate cancer. There were no significant differences in the incidence of radiation-induced pain flare; response to radiation; changes from baseline for BM22, C15-PAL; and DSQ, nor overall survival at day 42 between the 2 groups. Responders to radiation in the elderly group reported better improvement in physical and emotional domains when compared with nonresponders.In patients with cancer having bone metastases undergoing palliative radiotherapy, there was no significant difference in general with age in response to radiation and patient-reported outcomes. Palliative radiotherapy should be offered to elderly patients when needed.

The lapatinib–taxane combination led to shorter PFS than trastuzumab–taxane in HER2+ metastatic breast cancer. We investigated the prognostic and predictive effects of pretreatment serum HER2, CAIX, and TIMP-1. MA.31 accrued 652 patients; 537 (82%) were centrally confirmed HER2+. Biomarkers were categorized for univariate and multivariable predictive investigations with a median cut-point, ULN cut-points (15 ng/ml for HER2; 506 pg/ml for CAIX; 454 pg/ml for TIMP-1), and custom cut-points (30 and 100 ng/ml for HER2). Stratified step-wise forward Cox multivariable analysis examined continuous and categorical effects of biomarkers on PFS in the ITT and central HER2+ populations; central HER2+ biomarker results are shown. Serum was banked for 472 (72%) of 652 patients. Higher serum HER2 (>median; >15; >30; or >100 ng/ml; p = 0.05–0.002); higher CAIX (>median; >506 pg/ml; p = 0.02; p = 0.001); and higher TIMP-1 (> median; > 454 pg/ml; p = 0.001; p = 0.02) had shorter univariate PFS. In multivariable analysis, higher continuous TIMP-1 was associated with significantly shorter PFS: HR = 1.001 (95% CI = 1.00–01.002; p = 0.004). Continuous serum HER2 and CAIX were not significantly associated with PFS. HER2 of 15 ng/ml or higher had shorter PFS (p = 0.02); higher categorical CAIX had shorter PFS (p = 0.01–0.08). Interaction terms of HER2, CAIX, and TIMP-1 with treatment were not significant; the predictive test power was low. Higher levels of serum TIMP-1, CAIX, and HER2 were significant prognostic biomarkers of shorter PFS. We found no significant interaction between serum biomarkers and response to lapatinib versus trastuzumab. Evaluation of TIMP-1 and CAIX-targeted therapy in addition to HER2-targeted therapy appears warranted in patients with elevated serum levels of these biomarkers.

Accumulated evidence demonstrates that Japanese encephalitis virus (JEV) infection triggers endoplasmic reticulum (ER) stress and neuron apoptosis. ER stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) has been reported to induce apoptosis under acute or prolonged ER stress. However, the precise role of PERK in JEV-induced apoptosis and encephalitis remains unknown. Here, we report that JEV infection activates the PERK-ATF4-CHOP apoptosis pathway both in vitro and in vivo. PERK activation also promotes the formation of stress granule, which in turn represses JEV-induced apoptosis. However, PERK inhibitor reduces apoptosis, indicating that JEV-activated PERK predominantly induces apoptosis via the PERK-ATF4-CHOP apoptosis pathway. Among JEV proteins that have been reported to induce ER stress, only JEV NS4B can induce PERK activation. PERK has been reported to form an active molecule by dimerization. The coimmunoprecipitation assay shows that NS4B interacts with PERK. Moreover, glycerol gradient centrifugation shows that NS4B induces PERK dimerization. Both the LIG-FHA and the LIG-WD40 domains within NS4B are required to induce PERK dimerization, suggesting that JEV NS4B pulls two PERK molecules together by simultaneously interacting with them via different motifs. PERK deactivation reduces brain cell damage and encephalitis during JEV infection. Furthermore, expression of JEV NS4B is sufficient to induce encephalitis via PERK in mice, indicating that JEV activates PERK primarily via its NS4B to cause encephalitis. Taken together, our findings provide a novel insight into JEV-caused encephalitis. IMPORTANCE Japanese encephalitis virus (JEV) infection triggers endoplasmic reticulum (ER) stress and neuron apoptosis. ER stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) has been reported to induce apoptosis under acute or prolonged ER stress. However, whether the PERK pathway of ER stress response plays important roles in JEV-induced apoptosis and encephalitis remains unknown. Here, we found that JEV infection activates ER stress sensor PERK in neuronal cells and mouse brains. PERK activation induces apoptosis via the PERK-ATF4-CHOP apoptosis pathway upon JEV infection. Among the JEV proteins prM, E, NS1, NS2A, NS2B, and NS4B, only NS4B activates PERK. Moreover, activated PERK participates in apoptosis and encephalitis induced by JEV and NS4B. These findings provide a novel therapeutic approach for JEV-caused encephalitis.

Introduction Migration is a form of geographic or spatial mobility involving a change of usual residence between clearly defined geographic units (Edmonston & Michalowski, 2004). Migration is intertwined with geopolitics, trade and cultural exchange, and provides opportunities for States, businesses and communities to benefit enormously.International migration is a complex phenomenon that touches on a multiplicity of economic, social and security aspects affecting our daily lives in an increasingly interconnected world (McAuliffe & Ruhs, 2017). The United Nations Recommendations on Statistics of International Migration defines an international migrant as any person who has changed his or her country of usual residence, distinguishing between “short-term migrants” (those who have changed their country of usual residence for at least three months, but less than one year) and “long-term migrants” (those who have done so for at least one year) (DESA, 1998). Obviously, migrationhas bothpositive and negative impact on the migrants, their families,and also the sendingand receiving countries.The world is facing huge challenges of property development and the billions of individual’s still flat ligneous financial condition and are empty a lifetime of pleasure. Particularly, youth unemployment may be a major concern. Like other less developed countries, Pakistan is facing with issues of large financial condition and speedy increase in its labor migration(Kamrava & Babar, 2012) 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

With the development of marine resources, the USV (Unmanned Surface Vehicle) was widely used as a platform for autonomous navigation in the marine environment. In order to ensure the safe navigation of USV, this paper proposed a sea surface obstacle detection method based on probability graphical model and sea-sky-line. Our method utilized the SLIC algorithm to segment the sea surface image for image pre-processing. Then, we proposed the superpixel-based probability graphical model to segment the image, and the sea surface image would be divided into three main semantic regions and an obstacle region. Finally, we proposed a sea-sky-line detection algorithm. Based on this, obstacles within the sea-sky-line would be detected. The accuracy of this method has reached 82.1%, and the recall rate has reached 92.0%. The method can effectively avoid the interference of sea surface reflection and objects such as clouds in the sky, and has a good effect on the detection of obstacles.

To the editor: Multiple myeloma is often treated with high-dose melphalan chemotherapy followed by maintenance therapy with immunomodulatory agents aimed to delay disease progression and prolong survival. Although it is routinely offered to many patients, randomized trials of maintenance therapy

Quality of life (QOL) can be compromised in patients with bone metastases, and validated QOL instruments are required to accurately measure QOL outcomes in this population. This study investigated the validity, reliability and responsiveness of the EORTC QLQ-BM22 module with the EORTC QLQ-C15-PAL instrument in bone metastases.The studied patients underwent palliative radiotherapy to bone metastases in the randomized NCIC CTG SC 23 trial. Multi-trait scaling analysis was performed to determine convergent and divergent validity among scales. Pearson coefficients were calculated to determine the correlation between items of the two instruments. The clinical validity and responsiveness of the QLQ-BM22 was tested by known group comparisons of different performance status and response to radiotherapy.204 patients completed both questionnaires at baseline and 42day follow-up. On multi-trait scaling analysis, there was mixed evidence of construct validity (explained by the questionnaire format and population characteristics). There was little correlation between most QLQ-BM22 and QLQ-C15-PAL items (except for conceptually related scales) validating their complementary nature. There were statistically significant differences in all QLQ-BM22 scale scores in groups with KPS80 vs. KPS⩾80 and three out of four QLQ-BM22 scale scores in "responders" vs. "non-responders" to radiotherapy. In patients who responded to radiotherapy, there were statistically significant differences in all QLQ-BM22 scale scores between baseline and follow-up.This study further validates the use of the QLQ-BM22 as a robust and sensitive instrument to assess QOL in patients with bone metastases treated with palliative radiotherapy.

Objectives: To investigate the potential role of GABAB Receptors (GABABRs) involved in the effect of Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM) treatment on precocious puberty. Methods: Female Sprague-Dawley rats were randomly divided into four groups: normal (N), central precocious puberty (CPP) model (M), CPP fed with normal saline (S) and CPP fed with Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM). Rats of postnatal day 5 were given a single subcutaneous injection of 240 μg danazol to establish CPP model rats. Rats of S and TCM groups were continuously administered with saline or nourishing “Yin”-removing “Fire” Chinese herb mixture since postnatal day 15. The expression of GABABRs was detected by means of real-time PCR and immunohistochemistry. Results: The expression of hypothalamic GnRH mRNA in M was significantly increased on the day of pre-puberty when compared with that of N (P B1 receptor (GABABR1) immunoreactive cells in the arcuate nucleus (ARN) was decreased in M when compared with that of N (P B2 receptor (GABABR2) immunoreactive cells in the ARN, MS and diagnonal band of broca (DBB) were decreased in M when compared with those of N (P < 0.05) and increased in TCM compared with those of M (P < 0.05) on the day of onset-puberty. At the same time, the mRNA expression of GABABR2 was significantly decreased in M compared with that of N (P < 0.01). Conclusions: These results indicated that the GABABRs might involve in the curative effect of Nourishing “Yin”-Removing “Fire” Chinese herbal mixture on CPP rats.

The EORTC QLQ-C30 and the Brief Pain Inventory (BPI) are validated tools for measuring quality of life (QOL) and the impact of pain in patients with advanced cancer. Interpretation of these instrument scores can be challenging and it is difficult to know what numerical changes translate to clinically significant impact in patients’ lives. To address this issue, our study sought to establish the minimal clinically important differences (MCID) for these two instruments in a prospective cohort of patients with advanced cancer and painful bone metastases. Both anchor-based and distribution-based methods were used to estimate the MCID scores from patients enrolled in a randomized phase III trial evaluating two different re-irradiation treatment schedules. For the anchor-based method, the global QOL item from the QLQ-C30 was chosen as the anchor. Spearman correlation coefficients were calculated for all items and only those items with moderate or better correlation (|r| ≥ 0.30) with the anchor were used for subsequent analysis. A 10-point difference in the global QOL score was used to classify improvement and deterioration, and the MCID scores were calculated for each of these categories. These results were compared with scores obtained by the distribution-method, which estimates the MCID purely from the statistical characteristics of the sample population. A total of 375 patients were included in this study with documented pain responses and completed QOL questionnaires at 2 months. 9/14 items in the QLQ-C30 and 6/10 items in the BPI were found to have moderate or better correlation with the anchor. For deterioration, statistically significant MCID scores were found in all items of the QLQ-C30 and BPI. For improvement, statistically significant MCID scores were found in 7/9 items of the QLQ-C30 and 2/6 items of the BPI. The MCID scores for deterioration were uniformly higher than the MCIDs for improvement. Using the distribution-based method, there was good agreement between the 0.5 standard deviation (SD) values and anchor-based scores for deterioration. For improvement, there was less agreement and the anchor-based scores were lower than the 0.5 SD values obtained from the distribution-based method. We present MCID scores for the QLQ-C30 and BPI instruments obtained from a large cohort of patients with advanced cancer undergoing re-irradiation for painful bone metastases. The results from this study were compared to other similar studies which showed larger MCID scores for improvement compared to deterioration. We hypothesize that disease trajectory and patient expectations are important factors in understanding the contrasting results. The results of this study can guide clinicians and researchers in the interpretation of these instruments.

Background and purpose: Patient's gender and age may influence physicians in prescribing palliative radiotherapy. The purpose of this secondary analysis of the National Cancer Institute of Canada Clinical Trials Group Symptom Control Trial SC.20 was to explore the gender and age differences in pain and patient reported outcomes in cancer patients with bone metastases undergoing re-irradiation.Materials and methods: Response to radiation was evaluated using the International Bone Metastases Consensus Endpoint Definitions. Patients completed the Brief Pain Inventory (BPI) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (00) before and 2 months after re-irradiation.Results: A total of 847 patients were analyzed. At baseline, men had more dyspnea, and mild pain. Older patients consumed less analgesic. More women reported clinically significant improvement in mood and enjoyment of life in the BPI after radiation. Similarly, younger patients reported better improvement in enjoyment of life. There were no significant gender or age differences in overall survival, response to radiation, or in 00 scores at 2 months.Conclusion: Similar benefit in terms of pain relief was observed across all patient groups. Cancer patients with bone metastases should be offered palliative re-irradiation irrespective of gender or age. Trial Registration: NCT00080912; https://clinicaltrials.gov/ct2/show/NCT00080912. (C) 2017 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 126 (2018) 541-546

The objective of our study was to determine the optimal cut points for classification of pain scores as mild, moderate, and severe based on interference with function and quality of life (QOL). We evaluated 822 patients who completed the Brief Pain Inventory (BPI) and/or the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 30 (QLQ-C30) prior to receiving repeat radiation therapy for previously irradiated painful bone metastases. Optimal cut points for mild, moderate, and severe pain were determined by the MANOVA that yielded the largest F ratio for the between category effect on the seven interference items of BPI and the six functional domains of QOL (physical, role, emotional, cognitive, social functioning, and global QOL) as indicated by Pillai’s Trace, Wilk’s λ, and Hostelling’s Trace F statistics. For BPI and for QOL domains separately, the two largest F ratios for Wilk’s λ, Pillai’s Trace, and Hotelling’s Trace F statistics were from the cut points 4, 8 and 6, 8. When combining both, the optimal cut points were 4, 8 with 1–4 (mild), 5–8 (moderate), and 9–10 (severe). With this classification, the mean scores of all the seven interference items in BPI and the six functional domains were all highly statistically different. Patients with severe pain survived significantly shorter than those with mild and moderate pain (p

Background: For early high risk breast cancer, adjuvant chemotherapy following definitive surgery is a current standard of care. However, the optimal time to commencement of therapy has not been well established. We evaluated the association between time to initiation of adjuvant chemotherapy after definitive surgery (sTTC) with survival. Methods: We retrospectively analyzed 4 NCIC CTG-led breast cancer adjuvant clinical trials involving women diagnosed from 1984 and 2005 with stage 1 to 3 breast cancer, who received adjuvant chemotherapy. Patient data were categorized into four time groups: < 4, 4-8, >8-12, >12 weeks after definitive surgery. Outcomes measured were: overall survival (OS) and disease-free survival (DFS). Results: 3837 patients were included in the final analysis. In univariate analysis, an improvement was identified for patients treated between >8 and 12 weeks: Number of Pts10 yr OS(%)p-value10 yr DFS(%)p-value8-12 weeks74277.30.000272.60.0001>12 weeks3577.00.453173.90.2124 However, in multivariate analysis there was no significant association between any sTTC time periods and either outcome (see table below). Covariates which did show a significant association are listed in the table. OS p-valueDFS p-valueTime to Adjuvant 8-12 weeks0.42510.1396 >12 weeks0.68610.9312Age The fact that the statistical significance of sTTC in univariate analysis was lost when covariates related to DFS and OS were accounted for in a multivariate analysis suggested there might be a relationship between sTTC and the risk of adverse outcomes. A disease risk score analysis was therefore carried out, but there was no indication of an advantage to an earlier sTTC within disease risk categories. Conclusions: Within the context of chemotherapy given within 12 weeks, we were unable to demonstrate an effect on survival based on time to adjuvant chemotherapy in our multivariable analysis. Those treated later did not do significantly worse than those treated earlier. Significant covariates which effected survival were consistent with predictors of poor prognosis (younger age, poorer performance status, increased disease burden and receptor negativity). There is a potential relation of patient risk to time to treatment which requires further study. Citation Format: Ravi Ramjeesingh, Bingshu E Chen, Joseph L Pater, Liting Zhu, Margot Burnell, Vivien H Bramwell, Kathleen I Pritchard, Lois E Shepherd, Wendy R Parulekar. Association between definitive surgery and times to administration of adjuvant chemotherapy and outcomes in early breast cancer: Analysis of adjuvant studies conducted by NCIC Clinical Trials Group (NCIC CTG) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-09-02.