2,370 research outputs found
Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease.
No full textBACKGROUND: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
METHODS: In two double-blind, 52-week studies, ACCLAIM/COPD I (n=843) and II (n=804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1<80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation.
RESULTS: At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p<0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p<0.001). More patients had a SGRQ improvement≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p=0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p=0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p=0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p=0.9). Adverse events were minor in both studies.
CONCLUSION: Aclidinium is effective and well tolerated in patients with moderate to severe COPD
Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus
No full textAIM: To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy.METHODS: Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ? 2) with clinical stage T2-4 N0-1. Response to neoadjuvant chemotherapy (NAC) was assessed using TRG, as described by Mandard et al. In addition lymph node downstaging was also assessed. Lymph node downstaging was defined by cN1 at diagnosis: assessed radiologically (computed tomography, positron emission tomography, endoscopic ultrasonography), then pathologically recorded as N0 after surgery; ypN0 if NAC given prior to surgery, or pN0 if surgery alone. Patients were followed up for 5 years post surgery. Recurrence was defined radiologically, with or without pathological confirmation. An association was examined between t TRG and lymph node downstaging with disease free survival (DFS) and a comprehensive range of clinicopathological characteristics.RESULTS: Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years (median follow up: 2.552, 95%CI: 2.022-3.081). There was a 1.8% (n = 4) inpatient mortality rate. One hundred and thirty-six (62.4%) patients received NAC, with 74.3% (n = 101) of patients demonstrating some signs of pathological tumour regression (TRG 1-4) and 5.9% (n = 8) having a complete pathological response. Forty four point one percent (n = 60) had downstaging of their nodal disease (cN1 to ypN0), compared to only 15.9% (n = 13) that underwent surgery alone (pre-operatively overstaged: cN1 to pN0), (P < 0.0001). Response to NAC was associated with significantly increased DFS (mean DFS; TRG 1-2: 5.1 years, 95%CI: 4.6-5.6 vs TRG 3-5: 2.8 years, 95%CI: 2.2-3.3, P < 0.0001). Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC (median DFS; TRG 3-5 and nodal down-staging: 5.533 years, 95%CI: 3.558-7.531 vs TRG 3-5 and no nodal down-staging: 1.114 years, 95%CI: 0.961-1.267, P < 0.0001).CONCLUSION: Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS
Business Model Innovation of JF Logistics Company
No full text摘要 随着全球化经济的发展，市场竞争变得越来越复杂。信息时代使得物流供应链管理已上升到企业的战略管理高度。在这样的背景下，本文应用翁君奕老师的介观商务模式创新观点，对JF物流公司所处行业现状进行剖析，重新审视了外部客户市场以及内部自身情况，找出了JF物流公司自身的优势，并结合外部市场客户的需求，提出了“为客户提供个性化的集物流、资金流、信息流于一体的供应链物流服务”这一价值主张，并在此基础上，重新定位客户市场，创新服务产品，理顺内部管理架构和业务流程以支撑和保持这一价值主张。文中同时以例证来说明依据新价值主张所创新的服务产品给JF物流公司所带来的变化，以此说明通过商务模式创新来实行自身的战略...Abstract With the development of the global economy, the competition in market becomes more complicated. In the era of information, logistics and supply chain management is regarded as important as part of the company strategy. Under such background , the author of this essay uses the concept of “JieGuan Business Model Innovation” proposed by Professor Weng Junyi of Xiamen University, and analy...学位：管理学硕士院系专业：管理学院高级经理教育中心（EMBA项目）_管理经济学学号：X200615614
A systematic review of the association between pulmonary tuberculosis and the development of chronic airflow obstruction in adults
No full textIncludes abstract.Includes bibliographical references.Pulmonary tuberculosis (TB) as a cause of COPD is debated, with some, but not all evidence suggesting an association between the two conditions. Aim: To systematically review evidence for the association between pulmonary tuberculosis and the development of chronic obstructive pulmonary disease. We performed a systematic review of original English language, peer-reviewed literature using the PUBMED/MEDLINE database. Chronic Airflow Obstruction was defined on spirometric data (FEV1: FVC Ratio < 0.70; or FEV1: FVC Ratio < lower limit of normal for age, with or without bronchodilator use). Conclusions: Evidence was found for an association between a past history of tuberculosis and the presence of COPD. This association is independent of cigarette smoking. Causality is likely but cannot be assumed
Temporal and spatial variability in speakers with Parkinson's Disease and Friedreich's Ataxia
No full textSpeech variability in groups of speakers with Parkinson's disease (PD) and with Friedreich's ataxia was compared with healthy controls. Speakers repeated the same phrase 20 times at one of two rates (fast or habitual). A non-linear analysis of variability was performed which used some of the principles behind the spatio-temporal index (STI). The STI usually employs variation in lip displacement over repetitions of the same utterance and a linear analysis of such signals is conducted to represent the combined variation in spatial and temporal control. When working with patients, audio measures (here we used speech energy) are preferred over kinematics ones as they are minimally disruptive to speech. Non-linear methods allow spatial variability to be estimated separately from temporal variability. The results are tentatively interpreted as showing that PD speakers were distinguished from healthy control speakers in spatial variability and ataxic speakers were distinguished from controls in temporal variability. These findings are consistent with the speech symptoms reported for these disorders. We conclude that the non-linear analysis using the speech energy measure is worth investigating further as it is potentially revealing of the differences underlying these two pathologies
Additional file 6 of Prevalence of chronic cough in China: a systematic review and meta-analysis
No full textAdditional file 6. Fig. S1. Distribution of children with chronic cough across Mainland China. NOTE: Red star in the map represents Beijing City. The map was developed in XL Toolbox NG by ourselves, without the conflict of copyright. Fig. S2. Pooled chronic cough prevalence of adults stratified by region. Abbreviations: CI, confidence intervals. NOTE: The three author labels of ZHANG JF 1999 are from the same literature, and the two author labels of Venners 2001 are from the same literature. Fig. S3. Pooled chronic cough prevalence of adults stratified by diagnostic criteria. Abbreviations: CI, confidence intervals. NOTE: The three author labels of ZHANG JF 1999 are from the same literature, and the two author labels of Venners 2001 are from the same literature. Fig. S4. Pooled chronic cough prevalence of adults stratified by year of publication. Abbreviations: CI, confidence intervals. NOTE: The three author labels of ZHANG JF 1999 are from the same literature, and the two author labels of Venners 2001 are from the same literature. Fig. S5. Pooled chronic cough prevalence of adults stratified by age. Abbreviations: CI, confidence intervals. NOTE: The three author labels of ZHANG JF 1999 are from the same literature, and the two author labels of Venners 2001 are from the same literature. Fig. S6. Pooled chronic cough prevalence of adults stratified by sampling methods. Abbreviations: CI, confidence intervals. NOTE: The three author labels of ZHANG JF 1999 are from the same literature, and the two author labels of Venners 2001 are from the same literature. Fig. S7. Pooled chronic cough prevalence of adults stratified by sample size. Abbreviations: CI, confidence intervals; ES, Effect Size. NOTE: The three author labels of ZHANG JF 1999 are from the same literature, and the two author labels of Venners 2001 are from the same literature. Fig. S8. Pooled chronic cough prevalence of adults stratified by prevalence definitions. Abbreviations: CI, confidence intervals; ES, Effect Size. NOTE: The three author labels of ZHANG JF 1999 are from the same literature, and the two author labels of Venners 2001 are from the same literature. Fig. S9. Pooled chronic cough prevalence of adults stratified by chronic cough definitions. Abbreviations: CI, confidence intervals; ES, Effect Size. NOTE: The three author labels of ZHANG JF 1999 are from the same literature, and the two author labels of Venners 2001 are from the same literature. Fig. S10. Pooled chronic cough prevalence of adults stratified by quality of articles assessed by AHRQ. Abbreviations: CI, confidence intervals; ES, Effect Size. NOTE: The three author labels of ZHANG JF 1999 are from the same literature, and the two author labels of Venners 2001 are from the same literature. Fig. S11. Pooled chronic cough prevalence of children stratified by region. Abbreviations: CI, confidence intervals. NOTE: The four author labels of ZHANG JF 2002 are from the same literature. Fig. S12. Pooled chronic cough prevalence of children stratified by diagnostic criteria. Abbreviations: CI, confidence intervals. NOTE: The four author labels of ZHANG JF 2002 are from the same literature. Fig. S13. Pooled chronic cough prevalence of children stratified by year of publication. Abbreviations: CI, confidence intervals. NOTE: The four author labels of ZHANG JF 2002 are from the same literature. Fig. S14. Pooled chronic cough prevalence of children stratified by sample size. Abbreviations: CI, confidence intervals. NOTE: The four author labels of ZHANG JF 2002 are from the same literature. Fig. S15. Pooled chronic cough prevalence of children stratified by chronic cough definitions. Abbreviations: CI, confidence intervals; ES, Effect Size. NOTE: The four author labels of ZHANG JF 2002 are from the same literature. Fig. S16. Pooled chronic cough prevalence of children stratified by quality of articles assessed by AHRQ. Abbreviations: CI, confidence intervals. NOTE: The four author labels of ZHANG JF 2002 are from the same literature. Fig. S17. Pooled chronic cough prevalence of children stratified by prevalence definitions. Abbreviations: CI, confidence intervals. NOTE: The four author labels of ZHANG JF 2002 are from the same literature. Fig. S18. Funnel plot for prevalence in studies of adults for chronic cough. Fig. S19. Sensitivity analysis for prevalence in studies of adults for chronic cough. Abbreviations: CI, confidence intervals. NOTE: The three author labels of ZHANG JF 1999 are from the same literature, and the two author labels of Venners 2001 are from the same literature. Fig. S20. The prevalence of chronic cough in adults after exclusion of the nationwide study (Li JC 2018). Abbreviations: CI, confidence intervals. NOTE: The three author labels of ZHANG JF 1999 are from the same literature, and the two author labels of Venners 2001 are from the same literature. Fig. S21. The prevalence of chronic cough in adults after exclusion of the low prevalence study (ZHANG JF 1999). Abbreviations: CI, confidence intervals. NOTE: The two author labels of ZHANG JF 1999 are from the same literature, and the two author labels of Venners 2001 are from the same literature. Fig. S22. Funnel plot for prevalence in studies of children for chronic cough. Fig. S23. Sensitivity analysis for prevalence in studies of children for chronic cough. Abbreviations: CI, confidence intervals. NOTE: The four author labels of ZHANG JF 2002 are from the same literature. Fig. S24. Pooled prevalence of chronic cough in China (including adults and children). Abbreviations: CI, confidence intervals. NOTE: The three author labels of ZHANG JF 1999 are from the same literature, the two author labels of Venners 2001 are from the same literature, and the four author labels of ZHANG JF 2002 are from the same literature
Substitution of arginine for glycine 664 in the collagen α1(I) chain in lethal perinatal osteogenesis imperfecta. Demonstration of the peptide defect by in vitro expression of the mutant cDNA
No full textStructurally abnormal type I collagen was identified in tissues and cultured fibroblasts from a case of lethal perinatal osteogenesis imperfecta. Two-dimensional gel electrophoresis of the CNBr peptides demonstrated that the α1(I)CB7 peptide from the α1(I) chain of type I collagen existed in a normal form and a mutant form with a more basic charge distribution (Bateman, J.F., Mascara, T., Chan, D., and Cole, W.G. (1987) J. Biol. Chem. 262, 4445-4451). Sequencing of cloned α1(I) cDNAs prepared using mRNA from the patient's fibroblasts demonstrated that one clone had a single base substitution of A for G which resulted in the substitution of arginine for glycine 664 within the α1(I)CB7 peptide. To determine whether this mutation was responsible for the peptide map abnormality, in vitro transcription of mRNA from the mutant cDNA was performed using an SP6 vector system. The mRNA was then translated into mutant protein in a rabbit reticulocyte lysate. Peptide analysis of the protein produced from the mutant cDNA demonstrated the same altered charge distribution of the α1(I)CB7 peptide as observed with tissue- and cell-derived mutant collagen peptides. This finding confirmed that the arginine for glycine 664 sequence abnormality defined in the cDNA clone was the mutation causing the observed protein peptide map defect. This mutation is consistent with the functional abnormalities of collagen observed in this case such as reduced helical stability, reduced secretion, increased degradation, and excessive posttranslational modification of lysine.link_to_subscribed_fulltex
Joint faulting behaviour of innovative short concrete slabs
No full textPavements are one of the largest assets of a city and their functional condition (ride quality) is priority for their clients. In jointed plain concrete pavements (JPCPs), the presence of joint faulting (JF) reduces the ride quality. Today, short slabs are available as a cost-effective JPCP innovation. The objective of this paper is to analyse the JF behaviour of JPCPs with short slabs. For this, a deterioration model to predict it and trends of JF observed in short slabs of Chile and the United States are considered. The HDM-4 model always yields lower JF per joint in short slabs than in traditional ones. However, real-world short slabs show not only lower JF per joint (that the modelled JF), but also that more joints do not necessarily mean more JF per length of pavement that affect the ride quality. One of the relevant explanatory factors for it is the radical reduction of crack width at joints, which produces a fundamental increase of the load transfer efficiency. To maintain favourable behaviour observed in the field it is recommended to assure joint activation and to provide adequate stiffness of the layers below the short slabs.Pavement Engineerin
Metabolism of archidonic acid by 5-lipoxygenase in guinea-pig lung
No full textPT: J; CR: BURKA JF, 1981, PROSTAG OTH LIPID M, V22, P683 BURKA JF, 1983, J PHARMACOL EXP THER, V225, P427 PARKER CW, 1982, BIOCHEM BIOPH RES CO, V109, P1011 SAAD MH, 1983, PROSTAGLANDINS, V25, P741 SAAD MH, 1984, EUR J PHARMACOL, V100, P13 SCHIANTARELLI P, 1981, EUR J PHARMACOL, V73, P363; NR: 6; TC: 6; J9: PROSTAGLANDINS; PG: 2; GA: TU225Source type: Electronic(1
Interaction of Collagen α1(X) Containing Engineered NC1 Mutations with Normal α1(X) in Vitro: Implications for the molecular basis of schmid metaphyseal chondrodysplasia
No full textCollagen X is a short-chain homotrimeric collagen expressed in the hypertrophic zone of calcifying cartilage. The clustering of mutations in the carboxyl-terminal nonhelical NC1 domain in Schmid metaphyseal chondrodysplasia (SMCD) suggests a critical role for NC1 in collagen X structure and function. In vitrocollagen X DNA expression, using T7-driven coupled transcription and translation, demonstrated that although α1(X) containing normal NC1 domains can form electrophoretically stable trimers, engineered SMCD NC1 missense or premature termination mutations prevented the formation of electrophoretically stable homotrimers or heterotrimers when co-expressed with normal α1(X). To allow the detection of more subtle interactions that may interfere with assembly but not produce SDS-stable final products, we have developed a competition-basedin vitro co-expression and assembly approach. Our studies show that α1(X) chains containing SMCD mutations reduce the efficiency of normal α1(X) trimer assembly, indicating that interactions do occur between mutant and normal NC1 domains, which can impact on the formation of normal trimers. This finding has important implications for the molecular pathology of collagen X mutations in SMCD. Although we have previously demonstrated haploinsufficiency as one in vivo mechanism (Chan, D., Weng, Y. M., Hocking, A. M., Golub, S., McQuillan, D. J., and Bateman, J. F. (1998)J. Clin. Invest. 101, 1490–1499), the current study suggests dominant interference is also possible if the mutant protein is expressed in vivo. Furthermore, we establish that a conserved 13-amino acid aromatic motif (amino acids 589–601) is critical for the interaction between the NC1 domains, suggesting that this region may initiate assembly and the other NC1 mutations interfered with secondary interactions important in folding or in stabilizing the assembly process.link_to_OA_fulltex
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