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To investigate the anti-explosion behavior of high-strength reinforced concrete (RC) beam subjected to blast load, the ANSYS/LS-DYNA finite element analysis software was applied. Based on anti-explosion test results, the effects of reinforcement strength grade, reinforcement ratio and stirrup ratio on dynamic response, failure mode, resistance curve and ductility of RC beams under uniform blast load were studied. The anti-explosion performance of RC beam can be effectively improved by increasing the strength grade of the high-strength reinforcement. When the shear capacity is high enough, the ultimate capacity of high-strength RC beam can be significantly enhanced by increasing its reinforcement ratio. Anti-explosion performance may deteriorate due to the change of failure modes when the reinforcement ratio is increased to a certain extent. Increasing stirrup ratio can improve the shear capacity of high-strength RC beam to guarantee the full utilization of the advantage of high flexural capacity. For high-strength RC beam with sufficiently shear capacity, the further increase of stirrup ratio has a slight effect on the anti-explosion ability.

Surgery is becoming more practical and effective than conservative treatment in improving the poor outcomes of patients with breast cancer liver metastasis (BCLM). However, there is no generally acknowledged set of standards for identifying BCLM candidates who will benefit from surgery. Between January 2011 and September 2018, 67 female BCLM patients who underwent partial hepatectomy were selected for analysis in the present study. Prognostic factors after hepatectomy were determined. Univariate and multivariate analyses were performed to identify predictors of overall survival (OS) and intrahepatic recurrence-free survival (IHRFS). The 1-, 3- and 5-year OS of patients treated with surgery was 93.5%, 73.7% and 32.2%, respectively, with a median survival time of 57.59 months. The Pringle manoeuvre [hazard radio (HR) = 0.117, 95% CI0.015–0.942, p = 0.044] and an increased interval between breast surgery and BCLM diagnosis (HR0.178, 95% CI 0.037–0.869, p = 0.033) independently predicted improved overall survival for BCLM patients. The 1-, 2- and 3-year IHRFS of patients who underwent surgery was 62.8, 32.6% and 10.9%, respectively, with a median intrahepatic recurrence-free survival time of 13.47 months. Moderately differentiated tumours (HR 0.259, 95% CI 0.078–0.857, p = 0.027) and the development of liver metastasis more than 2 years after breast surgery (HR 0.270, 95% CI 0.108–0.675, p = 0.005) might be predictors of increased IHRFS. An interval of more than 2 years between breast cancer surgery and liver metastasis seems to be an indication of liver surgery in BCLM patients. The Pringle manoeuvre and moderately differentiated tumours are potential predictors associated with OS and IHRFS, respectively, as benefits from liver resection. Studies with increased sample sizes are warranted to validate our results.

Background Diabetes is considered as an established risk factor for cancer development. However, the link between diabetes among cancer survivors remains inconclusive. The hypothesis of this study was to assess the hazard ratio (HR) of incidence of diabetes in cancer survivors compared with the HR in the general population. Patients and Methods A comprehensive literature search was performed in PubMed, Embase, and the Cochrane Library from database inception to 15 December 2020 for population-based cohort studies. Summary effect estimates were combined using random-effects models. We also performed subgroup analyses to test sources of heterogeneity and the stability of the results stratified by various study and participant characteristics. Results Thirteen population-based cohort studies involving 1 686 595 participants were analyzed. The HR for the development of diabetes in cancer survivors was 1.39 [95% confidence interval (CI) 1.29-1.50; I2 = 82.3%; P < 0.001] compared with that in noncancer controls, among which survivors of hematological, gynecologic, breast, colorectal and urinary tract cancer (all P < 0.05) showed consistent significant results, whereas no significant increased risk was observed for other cancer types. The effects were more prominent in populations of shorter cancer survival duration (10 years) had a relatively higher risk of diabetes (HR 1.54, 95% CI 1.34-1.77) than those with a shorter follow-up period. Conclusions In this large pooled analysis of population-based cohorts, evidence supports the hypothesis that the risk of developing diabetes is increased in cancer survivors compared with the general population. We should interpret the results with caution for considerable interstudy heterogeneity. However, health policy makers should take this as a challenge for the early prevention and effective intervention of diabetes., Highlights • People previously diagnosed with cancer are at a higher risk of diabetes than the noncancer population. • Diabetes risk remains elevated for the majority of cancer types studied. • Shorter cancer survival duration and longer follow-up period are risk factors for diabetes. • Early prevention and effective intervention of diabetes among cancer survivors require attention.

Background In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab–paclitaxel in aTNBC. Patients and methods Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab–paclitaxel versus 5.7 months with placebo–paclitaxel]. In the PD-L1-positive population, atezolizumab–paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo–paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab–paclitaxel versus 28.3 months with placebo–paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. ClinicalTrials.gov NCT03125902.

This paper takes Guangxi coastal zone as the study area, following the standards of land use type, divides the coastal zone of ecological landscape into seven kinds of natural wetland landscape types such as woodland, farmland, grassland, water, urban land and wetlands. Using TM data of 2000–2015 such 15 years, with the CART decision tree algorithm, for analysis the characteristic of types of landscape’s remote sensing image and build decision tree rules of landscape classification to extract information classification. Analyzing of the evolution process of the landscape pattern in Guangxi coastal zone in nearly 15 years, we may understand the distribution characteristics and change rules. Combined with the natural disaster data, we use of landscape index and the related risk interference degree and construct ecological risk evaluation model in Guangxi coastal zone for ecological risk assessment results of Guangxi coastal zone.

This paper presents some preliminary results from research on monitoring the urban growth of Shenzhen in China. Agriculture is still the pillar of national economies in many countries including China. Thus, agriculture contributes to population growth. Population growth follows either exponential or logistic growth models. These models can be examined using a time-series of geospatial data, mainly historical earth observation imagery from satellites such as LANDSAT. Such multitemporal data may provide insights into settlement analysis as well as on population dynamics and hence, quantify the loss of agricultural land. In this study, LANDSAT data of ten dates, at approximately five yearly intervals from 1977 to 2017 were used. The remote sensing techniques used for analysis of data for 40 years were image selection, then followed by geometric and radiometric corrections and mosaicking. Also, classification, remote sensing image fusion, and change detection methods were used. This research extracted the information on the amount, direction, and speed of urbanization, and hence, the number of hectares of agricultural land lost due to urban expansion. Several specific elements were used in the descriptive model of landscape changes and population dynamics of the city of Shenzhen in China. These elements are: i) quantify the urban changes, from a small town (37.000 people in the early 1970’s) to the megalopolis of around 20 million habitants today. ii) Examining the rate of urban extension on the loss of agricultural landscape and population growth. iii) The loss of food production was analysed against the economic growth in the region. iv) The aspects of loss of agricultural land, area of built-up urban land, and increase in population are studied quantitatively, by the temporal analysis of earth observation geospatial data. The experimental results from this study show that the proposed method is effective in determining loss of agricultural land in any city due to urbanization. It can be used by town planner and other stakeholders such as land surveyors and agriculture experts to mitigate the mushrooming of unplanned settlements in many town / villages and loss of land for agriculture which might cause problems in food security.

Objectives Standard treatment for recurrent cervical cancer has not been established. To help improve management of the disease, this study presented clinicopathological features and identified prognostic factors in patients treated with secondary surgical resection and radiotherapy. Methods We retrospectively reviewed medical records of patients with recurrent cervical cancer confined to the pelvis during 2012 to 2017. This study only selected patients whose primary tumors were diagnosed at stage IIA2 or earlier, and received surgical resection for both primary and recurrent tumors. Their clinicopathological data were collected and analyzed. Cox regression models were applied to identify risk factors associated with post-recurrence survival. Results A total of 54 patients with recurrent cervical cancer were included. Thirty seven (68.5%) of recurrences occurred with 2 years after the initial treatment and 17 (31.5%)of them had tumor size >4 cm. Recurrences were treated with radical surgery plus pelvic radiotherapy. In addition, part of patients received vaginal radiotherapy (31.5%), concurrent chemotherapy (76.0%) and consolidated chemotherapy (37.0%). Chemoradiotherapy were administrated to 44.4% patients Conclusions After surgical resection plus radiotherapy, patients with recurrent cervical cancer confined to the pelvis have relatively high post-recurrence survival. Earlier start of chemoraidotherapy after secondary surgery and smaller recurrent tumors are associated with better post-recurrence survival.

Background & Aims Refractory gastroesophageal reflux disease (GERD) reduces quality of life and creates significant financial burden on the health care system. Approximately 30% of patients with GERD who receive label-dose proton pump inhibitors (PPIs) still have symptoms. We performed a trial to evaluate the efficacy and safety of IW-3718, a bile acid sequestrant, as an adjunct to PPI therapy. Methods We performed a multicenter, double-blind, placebo-controlled trial, from March 2016 through April 2017, of 280 patients with confirmed GERD. The patients, stratified by esophagitis status, were randomly assigned (1:1:1:1) to groups given placebo or IW-3718 (500, 1000, or 1500 mg) twice daily, with ongoing label-dose PPI. The primary endpoint was percent change from baseline to week 8 in weekly heartburn severity score. We also analyzed percent change from baseline to week 8 in weekly regurgitation frequency score. Results Mean changes from baseline to week 8 in weekly heartburn severity scores were reductions of 46.0% in the placebo group, 49.0% in the 500 mg group, 55.1% in the 1000 mg group, and 58.0% in the 1500 mg IW-3718 group (dose-response P = .02). The treatment difference was 11.9% between the 1500 mg IW-3718 and placebo groups (P = .04, analysis of covariance). The mean change in weekly regurgitation frequency score from baseline to week 8 in the 1500 mg IW-3718 vs placebo groups was a reduction of 17.5% (95% confidence interval, reductions of 31.4% to 3.6%). The most common adverse event was constipation (in 8.1% of patients receiving IW-3718 and 7.1% of patients receiving placebo). There were no drug-related serious adverse events. Conclusions In a randomized trial of patients with refractory GERD, adding 1500 mg IW-3718 to label-dose PPIs significantly reduced heartburn symptoms compared with adding placebo. Regurgitation symptoms also decreased. IW-3718 was well tolerated. ( ClinicalTrials.gov , Number: NCT02637557 )

BACKGROUND Fulvestrant is a selective estrogen receptor degrader (SERD) with no known agonist effects. In the open-label Phase 2 FIRST study, fulvestrant 500 mg suggested improved efficacy as first-line treatment vs anastrozole in patients with hormone receptor-positive locally advanced or metastatic breast cancer (LA/MBC). The Phase 3, randomized, double-blind, multicenter FALCON trial (NCT01602380) compared fulvestrant 500 mg with anastrozole 1 mg in patients with hormone receptor-positive LA/MBC who had not received prior hormonal therapy. The primary endpoint of the study, progression-free survival (PFS) assessed via RECIST 1.1, surgery/radiotherapy for disease worsening, or death (any cause), was met, as shown by a statistically significant improvement in PFS for fulvestrant 500 mg vs anastrozole. This analysis evaluated PFS in the Asian patient subgroup, which included all randomized patients from centers in China, Japan, and Taiwan. METHODS Eligible patients had ER and/or progesterone receptor-positive breast cancer, WHO performance status 0–2, and ≥1 measurable/non-measurable lesion(s). Patients were randomized (1:1) to receive fulvestrant 500 mg (IM on Days 0, 14, 28, and each 28 days thereafter) or anastrozole 1 mg daily, and were stratified according to LA or MBC; prior or no prior treatment with chemotherapy for LA/MBC; and measurable or non-measurable disease. The consistency of effect across patient subgroups was assessed via hazard ratios and 95% confidence intervals using a log-rank test. RESULTS In total, 462 patients were randomized (n=230 fulvestrant 500 mg; n=232 anastrozole). The Asian subgroup comprised 67 patients (n=34 fulvestrant 500 mg; n=33 anastrozole). PFS outcomes for the Asian and non-Asian subgroups are presented (Table). The most commonly reported adverse event (AE) was arthralgia (18.2% vs 12.1% of patients with fulvestrant 500 mg and anastrozole, respectively). The rate of AEs leading to discontinuation of treatment was 3.0% and 3.0%, respectively. CONCLUSIONS Based on a preliminary assessment of 67 patients, the treatment effect in the Asian patient subgroup from the FALCON trial appears to be broadly consistent with the non-Asian population. PFS in Asian and non-Asian patient subgroupsGeographic regionNumber of patients (%) with event Hazard ratio (95% CI) Fulvestrant 500 mg n=230Anastrozole n=232 Asia19/34 (55.9%)22/33 (66.7%)0.81 (0.44, 1.50)Non-Asia124/196 (63.3%)144/199 (72.4%)0.79 (0.62, 1.01) Citation Format: Shao Z, Ellis MJ, Robertson JFR, Grinsted LM, Fazal M, Noguchi S. Progression-free survival results in postmenopausal Asian women: Subgroup analysis from a phase 3 randomized trial of fulvestrant 500 mg vs anastrozole for hormone receptor-positive advanced breast cancer (FALCON) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-08-09.

BACKGROUND Improved efficacy was suggested for fulvestrant 500 mg, a selective estrogen receptor degrader (SERD), vs anastrozole as first-line treatment for hormone receptor-positive locally advanced or metastatic breast cancer (LA/MBC) in the open-label Phase 2 FIRST trial. The Phase 3, randomized, double-blind, multicenter FALCON trial (NCT01602380) compared fulvestrant 500 mg with anastrozole 1 mg in patients with hormone receptor-positive LA/MBC who had not received prior hormonal therapy. The primary endpoint of the study was met, such that there was a statistically significant improvement in progression-free survival (PFS) for fulvestrant 500 mg vs anastrozole. We present an analysis of PFS for pre-specified patient subgroups in the FALCON trial. METHODS Eligible patients had ER and/or progesterone receptor (PgR)-positive breast cancer, WHO performance status 0–2 and ≥1 measurable/non-measurable lesion(s). Patients were randomized (1:1) to receive fulvestrant 500 mg (IM on Days 0, 14, 28, and each 28 days thereafter) or anastrozole 1 mg daily. The primary endpoint was PFS, assessed via RECIST 1.1, surgery/radiotherapy for disease worsening, or death (any cause). PFS was evaluated in patient subgroups defined by pre-specified baseline covariates. The consistency of effect across patient subgroups was assessed via hazard ratios and 95% confidence intervals using a log-rank test. RESULTS Overall, 462 patients were randomized to treatment: 230 received fulvestrant 500 mg and 232 received anastrozole. PFS outcomes in each patient subgroup are presented in the Table. CONCLUSIONS This analysis of patient subgroups from the FALCON trial suggests that treatment effects were largely consistent across the subgroups analyzed with some possible exceptions (e.g. patients with visceral vs non-visceral disease). Further work is ongoing to understand the possible treatment effect in these subgroups. PFS in pre-specified patient subgroupsSubgroup Number of patients (%) with event Hazard ratio (95% CI) Fulvestrant 500 mg n=230 Anastrozole n=232 Breast cancer type Locally advanced11/28 (39.3%)14/32 (43.8%)0.79 (0.36, 1.73)Metastatic132/202 (65.3%)152/200 (76.0%)0.78 (0.62, 0.99)Prior chemotherapy for LA/MBC Yes31/36 (86.1%)33/43 (76.7%)1.08 (0.66, 1.77)No112/194 (57.7%)133/189 (70.4%)0.75 (0.59, 0.97)Geographic regiona US/Canada16/25 (64.0%)19/24 (79.2%)0.66 (0.34, 1.30)Non-US/Canada127/205 (62.0%)147/208 (70.7%)0.81 (0.64, 1.03)Measurable disease Yes124/193 (64.2%)143/196 (73.0%)0.76 (0.60, 0.97)No19/37 (51.4%)23/36 (63.9%)0.99 (0.53, 1.82)ER-positive and PgR-positive Yes103/175 (58.9%)127/179 (70.9%)0.73 (0.56, 0.94)No40/55 (72.7%)39/53 (73.6%)1.04 (0.67, 1.62)Bisphosphonate use at baseline Yes44/61 (72.1%)53/62 (85.5%)0.69 (0.46, 1.03)No99/169 (58.6%)113/170 (66.5%)0.82 (0.63, 1.07)Visceral disease Yes92/135 (68.1%)87/119 (73.1%)0.99 (0.74, 1.33)No51/95 (53.7%)79/113 (69.9%)0.59 (0.42, 0.84)ªData for Asia/non-Asia subgroups are presented in a separate abstract Citation Format: Robertson JFR, Noguchi S, Shao Z, Grinsted LM, Fazal M, Ellis MJ. Progression-free survival results in patient subgroups from a Phase 3 randomized trial of fulvestrant 500 mg vs anastrozole for hormone receptor-positive advanced breast cancer (FALCON) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-08-02.

Drought caused the most widespread damage in China, making up over 50 % of the total affected area nationwide in recent decades. In the paper, a Standardized Precipitation Index-based (SPI-based) drought risk study is conducted using historical rainfall data of 19 weather stations in Shandong province, China. Kernel density based method is adopted to carry out the risk analysis. Comparison between the bivariate Gaussian kernel density estimation (GKDE) and diffusion kernel density estimation (DKDE) are carried out to analyze the effect of drought intensity and drought duration. The results show that DKDE is relatively more accurate without boundary-leakage. Combined with the GIS technique, the drought risk is presented which reveals the spatial and temporal variation of agricultural droughts for corn in Shandong. The estimation provides a different way to study the occurrence frequency and severity of drought risk from multiple perspectives.

Background Endometrial cancer (EC) is one of the most common gynaecological tumours. Tumour mutational burden (TMB) has emerged as a promising predictor to evaluate efficacy to immunotherapy in several kinds of solid tumours. However, the relationship between TMB and genetic features of EC remains unclear. Methods Total 50 EC patients including 41 endometrioid adenocarcinoma, 6 uterine serous adenocarcinoma, 1 uterine clear cell carcinoma, 1 endometrial squamous cell carcinoma and 1 endometrial adenosquamous carcinoma were enrolled in this study. The ECs had been classified as FIGO I (n = 14), II (n = 6), III (n = 12), IV (n = 16) and not available (n = 2). FFPE tumour and matched blood samples were collected from patients for NGS-based targeted panel sequencing (450 genes). Genomic alterations and TMB were assessed. Results The 50 patients had a median age of 56 years (range, 32-73 years) with a median TMB of 3.8 muts/Mb (interquartile range (IQR), 1.5-13.7 muts/Mb). We found recurrent mutations, including PTEN (64%), PIK3CA (44%), ARID1A (40%), PIK3R1 (36%), TP53 (32%), CHD4 (20%), and KRAS (20%). FGFR2 mutations were occurred in 7 (14%) patients. The most frequently mutated genes in early-stage (FIGO I and II) were PTEN (85%), ARID1A (50%), PIK3R1 (50%), PIK3CA (40%), LRP1B (30%), and CHD4 (30%), while the most common mutations in advanced-stage (FIGO III and IV) were PTEN (46%), PIK3CA (43%), TP53 (43%), ARID1A (36%), PIK3R1 (29%), and KRAS (21%). We also found that all POLE mutations (5/5) occurred in early-stage. Mutations of PIK3R1, CHD4, CTCF, SETD2, PPP2R1A, NF1, BRCA2, ARID1B and POLE were associated with TMB-high (TMB-H, TMB≥10muts/Mb) (P 100 muts/Mb). At least one actionable mutation was identified in 86% (43/50) patients. Conclusions PI3K signaling pathway genes, PTEN, PIK3CA and PIK3R1 were most frequently mutated in EC. 26% patients (13/50) had TMB-H. POLE mutations likely occurred in early stage and were related with TMB-H, which may provide potential targets for immunotherapy of EC. Legal entity responsible for the study The authors. Funding National Natural Science Foundation of China (Youth fund project, no. 81602267). Disclosure Y. Zhang: Full / Part-time employment: OrigiMed. S. Zhang: Full / Part-time employment: OrigiMed. S. Zhao: Full / Part-time employment: OrigiMed. F. Guo: Full / Part-time employment: OrigiMed. F. Pang: Full / Part-time employment: OrigiMed. L. Zhang: Full / Part-time employment: OrigiMed. X. Dong: Full / Part-time employment: OrigiMed. K. Wang: Full / Part-time employment: OrigiMed. All other authors have declared no conflicts of interest.

Objectives This study aimed to examine the validity of the modified Reflux Symptom Questionnaire-electronic Diary (mRESQ-eD) through patient input and psychometric testing of the questionnaire to support use in clinical trials in patients with persistent gastroesophageal reflux disease (GERD) and in accordance with Food and Drug Administration guidance on patient-reported outcome instruments. Methods Cognitive interviews were conducted with patients (n = 30) to evaluate the interpretability and content validity of draft mRESQ-eD items. Patient data from a phase 2b clinical study (ClinicalTrials.gov identifier: NCT02637557) on persistent GERD served to aid in the construction of weekly scores for heartburn severity, regurgitation severity, and total GERD severity. These scores' psychometric properties were also evaluated. Results Minor modifications were made to the draft mRESQ-eD based on patient feedback to improve interpretability and clarity of the instrument. Psychometric analysis suggested that an 8-item version of the mRESQ-eD was best suited to the clinical data. The internal consistency was found to be high (Coefficient ω = 0.95). Retest reliability and convergent validity were strong for a heartburn weekly severity score, regurgitation weekly severity score, and total GERD severity score. Discussion The final 8-item mRESQ-eD is a reliable and valid instrument with good psychometric properties for use in clinical trials in patients with persistent GERD. The mRESQ-eD may be considered for inclusion in clinical trials for persistent GERD and potentially positioned, in consultation with Food and Drug Administration, as endpoints to characterize treatment benefit.

Summary Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine; for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement.

The dynamic response and failure characteristics of reinforced concrete beams under explosion loads are affected by various factors. To study the effect of reinforcement strength on the deformation properties of RC beams and to analyze the deformation differences of high-strength RC beams under different explosion loads, comparative explosion tests on two kinds of simply supported RC beams with longitudinal reinforcement yield strength of 400 MPa and 700 MPa were carried out respectively in this paper. The test results show that the deformation of the mid-span section concrete of the high-strength RC beam is basically the same as that of the ordinary RC beam when the peak overpressure value is small, and the strength advantage of the high-strength reinforcement has not been fully exerted. With the increase of explosion load, the maximum tensile strain and compressive strain of concrete at the mid-span section of high-strength RC beams are 46.6% and 43.5% of ordinary RC beams respectively. Under the action of high overpressure explosion load, the deformation of RC beams can be significantly reduced by high-strength reinforcement, which limits the development of cracks.

Background: To ascertain the current trends of breast reconstruction (BR) for breast cancer patients in China, we conducted a retrospective study in Committee of Breast Cancer Society, Chinese Anti-Cancer Association. Methods: We designed a questionnaire for this study, and it included questions on surgeon demographics, number of mastectomy and BR, type and timing of BR, reconstructive choices in the setting of preoperative or postoperative radiotherapy (RT) or chemotherapy, complication, oncoplastic surgery, fat grafting, physician and patient satisfaction, etc. All data were collected until 2012. Questionnaires were sent to 52 members of Committee of Breast Cancer Society by e-mail. By Jun-2013, 30 questionnaires (response rate 57.7%) had been returned. Among all, 3 were excluded for not performing BR. Finally, 27 respondents were included. Results: All but one of these 27 hospitals were Class Three Grade A hospitals in China. A total of 402 surgeons worked in the general surgery or oncological surgery department, among them, only 84 (20.9%) were able to perform BR. Surgeons from 10 hospitals would also choose to cooperate with the plastic department to finish the complicated reconstructive procedure. In 2012, 21026 mastectomies were performed; among them, 679 (3.2%) received immediate BR, 102 (0.5%) received delayed BR while 192 (0.9%) received delayed-immediate one. At the same time, 414 (2.0%) had their breast reconstructed by implant while 393 (1.9%) chose the autologous ones, the choices of reconstructive type were not recorded for other 166 (0.8%) cases. According to these 27 respondents, 88.9% predominantly performed prosthetic (1265 cases in all) or latissimus dorsi myocutaneous flap (LDMF) with or without an implant (1571 cases in all) BR from the time of their first BR operation to the end of 2012. During the same period, 327 pedicled transverse rectus abdominis myocutaneous (TRAM) BR were performed in 20 hospitals, while 169 free TRAM BR, which requiring technique of microsurgery, were carried out in 9 hospitals (68.6% were performed by a single surgeon from Nov-2006). The overall complication rate of BR was 12.4%. As RT had low to medium effect on increasing the operational difficulties and influencing the esthetic outcomes of BR, about 75% surgeons would choose delayed autologous BR in patients who had previous RT. Autologous flaps were also recommended for patients who need postoperative RT, but the timing still remained controversial. The overall cosmetic outcomes of the reconstructed breasts satisfied the majority of physicians and patients. Conclusion: With the growing number of breast cancer patients who need to undergo mastectomy, more and more BR are needed to improve the quality of life for them, but the ratio is still low in China, partially because of the lack of qualified plastic surgeons. As free flap BR requiring microsurgical techniques seems still complicated for most surgeons, implant and LDMF BR are the most common choices for patients nowadays in China. In addition, the effect of radiotherapy will be an important consideration when deciding the type and timing of BR. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-19-07.

Linaclotide is a minimally absorbed guanylate cyclase-C agonist. The objective of this trial was to determine the efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C).This phase 3, double-blind, parallel-group, placebo-controlled trial randomized IBS-C patients to placebo or 290 μ g oral linaclotide once daily in a 12-week treatment period, followed by a 4-week randomized withdrawal (RW) period. There were four primary end points, the Food and Drug Administration ’ s (FDA ’ s) primary end point for IBS-C (responder: improvement of ≥ 30 % in average daily worst abdominal pain score and increase by ≥ 1 complete spontaneous bowel movement (CSBM) from baseline (same week) for at least 50 % of weeks assessed) and three other primary end points, based on improvements in abdominal pain and CSBMs for 9 / 12 weeks. Adverse events (AEs) were monitored.The trial evaluated 800 patients (mean age = 43.5 years, female = 90.5 % , white = 76.9 % ). The FDA end point was met by 136 / 405 linaclotide-treated patients (33.6 % ), compared with 83 / 395 placebo-treated patients (21.0 % ) ( P0.0001) (number needed to treat: 8.0, 95 % confidence interval: 5.4, 15.5). A greater percentage of linaclotide patients, compared with placebo patients, reported for at least 6 / 12 treatment period weeks, a reduction of ≥ 30 % in abdominal pain (50.1 vs. 37.5 % , P = 0.0003) and an increase of ≥ 1 CSBM from baseline (48.6 vs. 29.6 % , P0.0001). A greater percentage of linaclotide patients vs. placebo patients were also responders for the other three primary end points ( P0.05). Significantly greater improvements were seen in linaclotide vs. placebo patients for all secondary end points ( P0.001). During the RW period, patients remaining on linaclotide showed sustained improvement; patients re-randomized from linaclotide to placebo showed return of symptoms, but without worsening of symptoms relative to baseline. Diarrhea, the most common AE, resulted in discontinuation of 5.7 % of linaclotide and 0.3 % of placebo patients.Linaclotide significantly improved abdominal pain and bowel symptoms associated with IBS-C for at least 12 weeks; there was no worsening of symptoms compared with baseline following cessation of linaclotide during the RW period.

Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase C receptor. In two trials, we aimed to determine the efficacy and safety of linaclotide in patients with chronic constipation.We conducted two randomized, 12-week, multicenter, double-blind, parallel-group, placebo-controlled, dual-dose trials (Trials 303 and 01) involving 1276 patients with chronic constipation. Patients received either placebo or linaclotide, 145 μg or 290 μg, once daily for 12 weeks. The primary efficacy end point was three or more complete spontaneous bowel movements (CSBMs) per week and an increase of one or more CSBMs from baseline during at least 9 of the 12 weeks. Adverse events were also monitored.For Trials 303 and 01, respectively, the primary end point was reached by 21.2% and 16.0% of the patients who received 145 μg of linaclotide and by 19.4% and 21.3% of the patients who received 290 μg of linaclotide, as compared with 3.3% and 6.0% of those who received placebo (P0.01 for all comparisons of linaclotide with placebo). Improvements in all secondary end points were significantly greater in both linaclotide groups than in the placebo groups. The incidence of adverse events was similar among all study groups, with the exception of diarrhea, which led to discontinuation of treatment in 4.2% of patients in both linaclotide groups.In these two 12-week trials, linaclotide significantly reduced bowel and abdominal symptoms in patients with chronic constipation. Additional studies are needed to evaluate the potential long-term risks and benefits of linaclotide in chronic constipation. (Funded by Ironwood Pharmaceuticals and Forest Research Institute; ClinicalTrials.gov numbers, NCT00765882 and NCT00730015.).

With the integration of large-scale wind power plants (WPPs), there is more and more demand for peak regulation service, and the peak regulation cost is increasing too. Reasonable calculation of peak regulation service cost caused by wind power generation (WPG) is the premise of stimulating conventional units to provide peak regulation services. After introducing the concept of peak regulation service in China, the impact of WPG on peak regulation is analyzed, and a quantitative model of peak regulation cost caused by WPG is put forward form the view point of the value of unit output adjustment. An optimization model with paid peak regulation is established to analyze the impact of WPG on peak regulation costs. The proposed method is tested on a 10-thermal power units system with WPPs, and the results verify the effectiveness of the proposed method.

Higher expression of heat shock protein 72 (HSP72) reduces the mortality rate and organ damage in septic shock and prevents cardiac mitochondrial dysfunction due to lipopolysaccharide (LPS). Our hypothesis is that exercise preconditioning may increase the expression of HSP72 in heart and the nucleus tractus solitarii (NTS) of the brain to alleviate the cardiovascular dysfunction in type I diabetic rats receiving endotoxin. Wistar rats were randomly assigned to the following groups: sedentary normal, sedentary type I diabetic rats, and type I diabetic rats with exercise training. The trained rats ran on a treadmill 5 d·week–1, 30–60 min·d–1, at an intensity of 1.0 mile·h–1 (1 mile = 1.6 km) over a 3 week period. Twenty-four hours after the last training session, we compared the temporal profiles of mean arterial pressure, heart rate, cardiac output, stroke volume, and serum tumor necrosis factor α level in rats receiving an injection of LPS. In addition, HSP72 expression in heart and NTS from each group was determined. We found that HSP72 expression in the heart and NTS was significantly increased in diabetic rats with exercise training. After administration of LPS, the survival time was significantly longer in diabetic rats with exercise training. Additionaly, serum tumor necrosis factor α levels decreased as compared with those rats not receiving exercise training. Exercise training also diminished cardiovascular dysfunction in diabetic rats during endotoxemia. These data suggest that exercise may increase the expression of HSP72 in the heart and NTS to protect against the high mortality rate and attenuate cardiovascular dysfunction in diabetic rats during endotoxemia.

Background and purpose: Ischaemia damages to the cardiac mitochondria by increasing generation of reactive oxygen species (ROS) and peroxidation of cardiolipin. The inhibited mitochondrial function leads to the cardiac injury during reperfusion. Propofol (2, 6-diisopropylphenol), an intravenous anaesthetic, has been shown to decrease cardiac ischaemia and reperfusion injury. In the present study, we propose that propofol protects mitochondrial function and decreases cardiac injury by prevention of cardiolipin peroxidation during ischaemia and reperfusion.

Nd:LuVO4 crystal was used for the most compact and the simplest laser, i.e. the microchip construction. LD (laser diode)-pumped, continuous-wave output property was detected on several Nd:LuVO4 microchips with different Nd3+ doping level, crystal length, and transmittance of output surface. With a 0.5 at.%, 1.5 mm, T = 1% crystal, 9.7 W maximum output was achieved, corresponding an optical-optical conversion efficiency of 32.0%. With a 1 at.%, 1.5 mm, T = 1% crystal, 9.1 W maximum output was achieved at a pump power of 20.5 W, which had the highest optical-optical conversion efficiency of 44.4%.

The open computational fluid dynamics (CFD) code called Gerris is very popular recently for its grid discretising strategy using quad/octree. It is available to numerically simulate a large range of problems in fluid domains and the simulation preprocess of grid is easy to represent the complex solid boundary by means of volume of fluid (VOF) approach. Two classical two-dimensional (2D) bluff and streamlined bodies, namely circle cylinder and airfoil NACA2414, are simulated firstly with various Reynolds numbers and grid resolutions. The DNS results in this paper are validated based on the criteria of the force coefficient convergence with various grid levels. The three-dimensional (3D) floating sphere and series 60 ship hull are also simulated including the water free surface and induced wave with various Froude numbers and the results are validated employing the same previous processes. The results show that the force coefficients acted on the bluff bodies without water surface cannot easily converge to steady ones even with fine grids of high resolutions. Comparatively, the force coefficient of the streamlined body without water free surface is easier to converge even with turbulent flow. The results of 3D computational cases with water free surface show that the force coefficients would converge to desirable ones with grid level 8 and 9 both for the series 60 ship hull and the floating sphere, which are bluff body and streamlined body, respectively. Generally, Gerris is very suitable for calculating the cases with water free surface with relative low grid resolution.

A novel grating is proposed to produce multi-wavelength output with inscribing phase-shifted fiber Bragg grating (FBG) in polarization-maintaining fiber (PMF). The reflective spectrum of grating is analyzed by a transfer matrix method. The effects of grating parameters on property of the phase-shifted FBG in PMF are discussed. We find that optimistic phase-shifted FBG in PMF with high reflective peaks, narrow bandwidths and multi-wavelength is possible if the grating parameters are properly selected.

Summary In recent years we have observed that some patients with idiopathic cytopenia of undetermined significance (ICUS) responded well to corticosteroid and high-dose intravenous immunoglobulin treatment, indicating that some cytopenia in ICUS might be mediated by autoantibodies. In this study, we analysed 166 ICUS cases retrospectively, some of which were autoantibodies detected on haemopoietic cells in bone marrow (BM) by BM mononuclear cell (BMMNC)-Coombs test, flow cytometry (FCM), Western blot and immunofluorescence (IF). We found that 25·9% (43 of 166) of the cases had autoantibodies positive verified with BMMNC-Coombs test or FCM analysis, 72·1% (31 of 43) of whom had immunoglobulin (Ig)G autoantibody positive by Western blot. IgG could be detected in the erythroblastic islands on the BM smear of nine (32·1%, nine of 28) ICUS patients with autoantibodies by IF. Of these 43 patients, the median percentage of reticulocytes was 1·79%. More than half the patients had hyper-BM cellularity with a higher percentage of nucleated erythroid cells in the sternum. Total response rates to immunosuppressive therapy at 6, 12, 24 and > 36 months were 46·5% (20 of 43), 75% (30 of 40), 77·4% (24 of 31) and 66·7% (16 of 24), respectively. We termed this group of ICUS cases with autoantibodies as immunorelated haemocytopenia (or BMMNC-Coombs test-positive haemocytopenia).

This paper presents the experimental results of two-wave mixing and self-pumped phase conjugation (SPPC) in barium titanate (BaTiO3) crystals doped with Rh or Ce. It has been shown that the main parameters of SPPC depend very strongly on the concentrations of dopants, the incident angles and the crystal cut used. High gain in two-wave mixing corresponds to low phase-conjugate reflectivity in all samples. It is impossible to maintain the highest reflectivity and gain simultaneously, because the gain will definitely be limited when we try to get the highest reflectivity, and vice versa. Some qualitative explanation of the experimental results is also given.

A method of determining the spatial configuration of a YCa4O(BO3)3 (YCOB) crystal is introduced. The type-I phase-matching points for the sum-frequency of 1.064 μm and 0.532 μm, as well as the conversion efficiency for YCOB samples cut in different directions, have been measured. When the input intensity is 0.76 GW/cm2, the third-harmonic generation (THG) conversion efficiency for the (106°, 77.2°)-cut YCOB crystal reaches 26.2%, which is the highest that we know so far. Both the calculations and the experiments show that the optimum THG configuration for a YCOB crystal is near (106°, 77.2°), or other equivalent directions in space.

A diode-laser-array end-pumped acousto-optically Q-switched intracavity frequency-doubled Nd:GdVO4/KTP green laser, formed with a three-mirror folded resonator, has been demonstrated. With 15 W of pump power incident upon the Nd:GdVO4 crystal, a maximum average green output power of 3.75 W was obtained at 50 kHz of pulse repetition frequency, giving an optical conversion efficiency of 25%, whereas the effective intracavity frequency-doubling efficiency was determined to be 72%. At the incident pump power of 12.8 W, the shortest laser pulse was achieved at a pulse repetition rate of 10 kHz, the resulting pulse width, single pulse energy, and peak power were measured to be 35 ns, 108 μJ, and 3.1 kW, respectively.

In systemic autoimmune-prone (NZB × NZW)F1 (NZB/W F1) mice, B-cell abnormalities characterized by hypergammaglobulinaemia accompanying autoantibodies have been thought to be a main cause of the disease. To examine a possible regulatory role of B cells in the disease manifestations, we injected, intravenously (i.v.), normal or autoimmune B cells into non-irradiated NZB/W F1 mice. The injection of splenic B cells from major histocompatibility (MHC)-matched or allogeneic normal mice caused a marked decrease in serum immunoglobulin G (IgG) levels of autoantibodies, delayed the appearance of proteinuria and prolonged life span, whereas treatment with splenic B cells from NZB/W F1 or X-linked immunodeficient (Xid) mice failed to suppress the autoimmunity. Moreover, in vitro polyclonal antibody responses to lipopolysaccharide (LPS) of NZB/W F1-derived B cells from the treated mice were markedly reduced. Interestingly, the treatment of NZB/W F1 mice at 16, 18 and 20 or at 20, 22 and 24 weeks of age was more effective than that at 6, 8 and 10 weeks. The treatment also inhibited the development of surface IgG+ (sIgG+) B cells and splenomegaly, prominent in aged NZB/W F1 mice. In addition, when untreated NZB/W F1 responding B cells were precultured with normal B cells in vitro for 3 days, they also diminished the autoantibody production to subsequent LPS stimulation. Hence, the present results imply a novel function of normal B cells to ameliorate autoimmune disease in NZB/W F1 mice by correcting their B-cell abnormalities, and indicate that NZB/W F1 and Xid mice possess defects in this regulatory B-cell function.

The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy. It refined its earlier approach to the classification and management of luminal disease in the absence of amplification or overexpression of the Human Epidermal growth factor Receptor 2 (HER2) oncogene, while retaining essentially unchanged recommendations for the systemic adjuvant therapy of HER2-positive and 'triple-negative' disease. The Panel again accepted that conventional clinico-pathological factors provided a surrogate subtype classification, while noting that in those areas of the world where multi-gene molecular assays are readily available many clinicians prefer to base chemotherapy decisions for patients with luminal disease on these genomic results rather than the surrogate subtype definitions. Several multi-gene molecular assays were recognized as providing accurate and reproducible prognostic information, and in some cases prediction of response to chemotherapy. Cost and availability preclude their application in many environments at the present time. Broad treatment recommendations are presented. Such recommendations do not imply that each Panel member agrees: indeed, among more than 100 questions, only one (trastuzumab duration) commanded 100% agreement. The various recommendations in fact carried differing degrees of support, as reflected in the nuanced wording of the text below and in the votes recorded in supplementary Appendix S1, available at Annals of Oncology online. Detailed decisions on treatment will as always involve clinical consideration of disease extent, host factors, patient preferences and social and economic constraints., SCOPUS: ar.j, info:eu-repo/semantics/published

Nearly a century after Einstein first predicted the existence of gravitational waves, a global network of Earth-based gravitational wave observatories1,2,3,4 is seeking to directly detect this faint radiation using precision laser interferometry. Photon shot noise, due to the quantum nature of light, imposes a fundamental limit on the attometre-level sensitivity of the kilometre-scale Michelson interferometers deployed for this task. Here, we inject squeezed states to improve the performance of one of the detectors of the Laser Interferometer Gravitational-Wave Observatory (LIGO) beyond the quantum noise limit, most notably in the frequency region down to 150 Hz, critically important for several astrophysical sources, with no deterioration of performance observed at any frequency. With the injection of squeezed states, this LIGO detector demonstrated the best broadband sensitivity to gravitational waves ever achieved, with important implications for observing the gravitational-wave Universe with unprecedented sensitivity Fil: Aasi, J.. California Institute of Technology; Estados Unidos Fil: Abadie, J.. California Institute of Technology; Estados Unidos Fil: Abbott, P.. California Institute of Technology; Estados Unidos Fil: Abbott, R.. California Institute of Technology; Estados Unidos Fil: Abbott, T. D.. State University of Louisiana; Estados Unidos Fil: Kozameh, Carlos Nicolas. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Winkelmann, L.. Max Planck Institut f¨ur Gravitationsphysik; Alemania. Leibniz Universit¨at Hannover; Alemania Fil: Winkler, W.. Max Planck Institut f¨ur Gravitationsphysik; Alemania. Leibniz Universit¨at Hannover; Alemania Fil: Wip, C. C.. Massachusetts Institute of Technology; Estados Unidos Fil: Wittel, H.. Max Planck Institut f¨ur Gravitationsphysik; Alemania. Leibniz Universit¨at Hannover; Alemania Fil: Woan, G.. University of Glasgow; Reino Unido Fil: Wooley, R.. Livingston Observatory; Estados Unidos Fil: Worden, J.. Hanford Observatory; Estados Unidos Fil: Yablon, J.. Northwestern University; Estados Unidos Fil: Yakushin, I.. Livingston Observatory; Estados Unidos Fil: Yamamoto, H.. California Institute of Technology; Estados Unidos Fil: Yancey, C. C.. University of Maryland; Estados Unidos Fil: Yang, H.. Caltech-CaRT; Estados Unidos Fil: Yeaton Massey, D.. California Institute of Technology; Estados Unidos Fil: Yoshida, S.. Southeastern Louisiana University; Estados Unidos Fil: Yum, H.. Northwestern University; Estados Unidos Fil: Zanolin, M.. Embry-Riddle Aeronautical University; Estados Unidos Fil: Zhang, F.. Massachusetts Institute of Technology; Estados Unidos Fil: Zhang, L.. California Institute of Technology; Estados Unidos Fil: Zhao, C.. University of Western Australia; Australia Fil: Zhu, H.. State University of Pennsylvania; Estados Unidos Fil: Zhu, X. J.. University of Western Australia; Australia Fil: Zotov, N.. Louisiana Tech University; Estados Unidos Fil: Zucker, M. E.. Massachusetts Institute of Technology; Estados Unidos Fil: Zweizig, J.. California Institute of Technology; Estados Unidos

The influence of four sets of multiple reflection waves from self-pumped phase conjugators with doped (K0.5Na0.5)0.2(Sr0.75Ba0.25)0.9Nb2O6 photorefractive crystals on the conjugation fidelity is analyzed in presence of pyroelectric effect and photovoltaic effect. Some proposals to improve the conjugation fidelity of a self-pumped phase conjugator are demonstrated. The multiple reflection waves and their dynamic features are observed and analyzed.

Background: This Phase III, randomised, double-blind, multicentre trial (FALCON; NCT01602380) compared the selective estrogen receptor (ER) degrader (SERD) fulvestrant with anastrozole in patients with ER- and/or progesterone receptor-positive locally advanced or metastatic breast cancer who had not received prior hormonal therapy. Methods: Patients were randomised 1:1 to fulvestrant (500 mg IM on Days 0, 14, 28, then each 28 days) or anastrozole (1 mg daily). The primary endpoint was progression-free survival (PFS), assessed via RECIST 1.1, surgery/radiotherapy for disease worsening, or death. Secondary endpoints were: overall survival (OS); objective response rate (ORR, complete response [CR] or partial response [PR]); duration of response (DoR); expected DoR (EDoR); clinical benefit rate (CBR; CR, PR, or stable disease ≥24 weeks); duration of clinical benefit (DoCB); expected DoCB (EDoCB); health-related quality of life (HRQoL); and safety.