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产业与环境 1993年第1期15卷 48-51页

作者： n.p.vandenberg 陈定茂鹿特丹市港口管理局莱茵河研究项目

莱茵河研究项目（pOR）是荷兰正在进行的关于莱茵河的两个重要环境项目之一,另一个是莱茵河行动计划。鹿特丹市政府于1984年开始这个莱茵河研究项目,试图通过与排放者协商来治理上游污染源。到2002年,即斯拉夫特污泥场将要填满的年份,... 详细信息

莱茵河研究项目（pOR）是荷兰正在进行的关于莱茵河的两个重要环境项目之一,另一个是莱茵河行动计划。鹿特丹市政府于1984年开始这个莱茵河研究项目,试图通过与排放者协商来治理上游污染源。到2002年,即斯拉夫特污泥场将要填满的年份,某些污染物质的排放要被削减的百分率相当于疏浚污泥为允许倾入海中而截至2002年必须改善的百分率。在实现了这样一种削减的情况下,这些物质可视为属于Ⅰ类,也有关于Ⅱ类、Ⅲ类和Ⅳ类物质的规定。环境责任法的若干方面尚不清楚,但这个领域正在加紧研究。

关键词：莱茵河环境保护

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Supramolecular approaches for insulin stabilization without prolonged duration of action

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Acta pharmaceutica Sinica B 2023年第5期13卷 2281-2290页

作者： Rolande Meudom Yanxian Zhang Michael A.vandenberg Lei Zou Yi Wolf Zhang Matthew J.Webber Danny Hung-Chieh Chou Division of Endocrinology and Diabetes Department of PediatricsSchool of MedicineStanford UniversityPalo AltoCA 94305USA Department of Biochemistry School of MedicineUniversity of UtahSalt Lake CityUT 84112USA Department of Chemical Engineering University of Notre DameNotre DameIN 46556USA

Aggregation represents a significant challenge for the long-term formulation stability of insulin *** supramolecular pEGylation of insulin with conjugates of cucurbit[7]uril and polyethylene glycol(CB[7]-pEG)has been shown to stabilize insulin formulations by reducing aggregation *** prolonged in vivo duration of action,arising from sustained complex formation in the subcutaneous depot,limits the application scope for meal-time insulin uses and could increase hypoglycemic risk several hours after a *** affinity of CB[7]in binding the B1-phe residue on insulin is central to supramolecular pEGylation using this ***,here we synthesized n-terminal acid-modified insulin analogs to reduce CB[7]interaction affinity at physiological pH and reduce the duration of action by decreasing the subcutaneous depot effect of the *** insulin analogs show weak to no interaction with CB[7]-pEG at physiological pH but demonstrate high formulation stability at reduced ***,n-terminal modified analogs have in vitro and in vivo bioactivity comparable to native ***,in a rat model of diabetes,the acid-modified insulin formulated with CB[7]-pEG offers a reduced duration of action compared to native insulin formulated with CB[7]-*** work extends the application of supramolecular pEGylation of insulin to achieve enhanced stability while reducing the risks arising from a subcutaneous depot effect prolonging in vivo duration of action.

关键词： Diabetes mellitus Insulin aggregation Supramolecular pEGylation Selective n-Terminal modification n-terminal acid-modified insulin Subcutaneous depot Hypoglycemia Subcutaneous administration

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Competing risks of death in younger and older postmenopausal breast cancer patients

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World Journal of Clinical Oncology 2014年第5期5卷 1088-1096页

作者： Judy-Anne W Chapman Kathleen I pritchard paul E Goss James n Ingle Hyman B Muss Susan F Dent Ted A vandenberg Brian Findlay Karen A Gelmon Carolyn F Wilson Lois E Shepherd Michael n pollak nCIC Clinical Trials Group Queen's University Kingston ON K7L 3N6 Canada Sunnybrook Odette Cancer Centre University of Toronto Toronto ON M4N 3M5 Canada Massachusetts General Hospital Harvard University Boston MA 02114 United States Mayo Clinic Rochester MN 55902 United States Lineberger Comprehensive Cancer Center at the University of north Carolina at Chapel Hill Chapel Hill NC27514 United States Ottawa Hospital Cancer Center University of Ottawa Ottawa ON K1H8L6 Canada London Health Sciences Centre University of Western Ontario London ON N6G 2V4 Canada niagara Health System McM aster University St. Catharines ON L2R 2Z4 Canada BC Cancer Agency University of British Columbia Vancouver BC V5Z 1L3 Canada nCIC Clinical Trials Group Queen's University Kingston Ontario K7L 3N6 Canada Lady Davis Institute Jewish General Hospital McG ill University Montreal QC H3T 1E2 Canada

AIM: To show a new paradigm of simultaneously testing whether breast cancer therapies impact other causes of death. METHODS: MA.14 allocated 667 postmenopausal women to 5 years of tamoxifen 20 mg/daily ± 2 years of octreotide 90 mg, given by depot intramuscular injections monthly. Event-free survival was the primary endpoint of MA.14; at median 7.9 years, the tamoxifen+octreotide and tamoxifen arms had similar event-free survival(p = 0.62). Overall survival was a secondary endpoint, and the two trial arms also had similar overall survival(p = 0.86). We used the median 9.8 years follow-up to examine by intention-to-treat, the multivariate time-to-breast cancer-specific(Br Ca) and other cause(OC) mortality with log-normal survival analysis adjusted by treatment and stratification factors. We tested whether baseline factors including Insulin-like growth factor 1(IGF1), IGF binding protein-3, C-peptide, body mass index, and 25-OH vitamin D were associated with(1) all cause mortality, and if so; and(2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted ***: The analyses were performed on 329 patients allocated tamoxifen and 329 allocated tamoxifen+octreotide. The median age of MA.14 patients was 60.1 years: 447(82%) nd 120(18%) ≥ 70 years. There were 170 deaths: 106(62.3%) BrC a; 55(32.4%) OC, of which 24 were other malignancies, 31 other causes of death; 9(5.3%) patients with unknown cause of death were excluded from competing risk assessments. BrC a and OC deaths were not significantly different by treatment arm(p = 0.40): tamoxifen patients experienced 50 BrC a and 32 OC deaths, while tamoxifen + octreotide patients experienced 56 Br Ca and 23 OC deaths. proportionately more deaths(p = 0.004) were from BrC a for patientspared to 54% for those ≥ 70 years of age. The proportion of deaths from OC increased with increasing body mass index(BMI)(p = 0.02). Higher pathol

关键词： Breast cancer postmenopausal Hormone receptor positive Competing risks Tamoxifen Octreotide LAR

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