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81.
Eric A.J. Bleeker Wim H. de Jong Robert E. Geertsma Monique Groenewold Evelyn H.W. Heugens Marjorie Koers-Jacquemijns Dik van de Meent Jan R. Popma Anton G. Rietveld Susan W.P. Wijnhoven Flemming R. Cassee Agnes G. Oomen 《Regulatory toxicology and pharmacology : RTP》2013,65(1):119-125
In recent years, an increasing number of applications and products containing or using nanomaterials have become available. This has raised concerns that some of these materials may introduce new risks for humans or the environment. A clear definition to discriminate nanomaterials from other materials is prerequisite to include provisions for nanomaterials in legislation. In October 2011 the European Commission published the ‘Recommendation on the definition of a nanomaterial’, primarily intended to provide unambiguous criteria to identify materials for which special regulatory provisions might apply, but also to promote consistency on the interpretation of the term ‘nanomaterial’. In this paper, the current status of various regulatory frameworks of the European Union with regard to nanomaterials is described, and major issues relevant for regulation of nanomaterials are discussed. This will contribute to better understanding the implications of the choices policy makers have to make in further regulation of nanomaterials. Potential issues that need to be addressed and areas of research in which science can contribute are indicated. These issues include awareness on situations in which nano-related risks may occur for materials that fall outside the definition, guidance and further development of measurement techniques, and dealing with changes during the life cycle. 相似文献
82.
83.
Lgr5 was originally discovered as a common Wnt target gene in adult intestinal crypts and colon cancer. It was subsequently identified as an exquisite marker of multiple Wnt-driven adult stem cell types. Lgr5 and its homologs, Lgr4 and Lgr6, constitute the receptors for R-spondins, potent Wnt signal enhancers and stem cell growth factors. The Lgr5/R-spondin complex acts by neutralizing Rnf43 and Znrf3, two transmembrane E3 ligases that remove Wnt receptors from the stem cell surface. Rnf43/Znrf3 are themselves encoded by Wnt target genes and constitute a negative Wnt feedback loop. Thus, adult stem cells are controlled by an intricate interplay of potent Wnt agonists, antagonists, and anti-antagonists. 相似文献
84.
Oxidation is a common degradation pathway that affects therapeutic proteins and peptides during production, purification, formulation, transportation, storage and handling of solid and liquid preparations. In the present work we review the scientific literature about structural and biological consequences of protein/peptide oxidation. Representative examples are discussed of specific products whose oxidation has been recently studied, including monoclonal antibodies, calcitonin, granulocyte colony-stimulating factor, growth hormone, insulin, interferon alpha and beta, oxytocin and parathyroid hormone. These examples illustrate that oxidation often leads to modifications of higher-order structures, including aggregate induction, and can generate products that are pharmacokinetically different, biologically less active and/or potentially more immunogenic than their native counterpart. It is therefore crucially important during the pharmaceutical development of therapeutic proteins and peptides to comprehensively characterize oxidation products and evaluate the impact of oxidation-induced structural modifications on the biological properties of the drug. 相似文献
85.
Little is known about the outcomes of food assistance targeted to food insecure people living with HIV/AIDS. Using primary data from Zambia, we estimated the impact of food assistance on the dietary diversity and consumption expenditures of households with HIV infected members receiving antiretroviral therapy. Propensity score matching estimates show that food assistance increased dietary diversity by 9.8 points (23%) mainly through the consumption of food items provided in the ration. Food assistance recipients were 20% points more likely to have acceptable food consumption and 15% points less likely to have poor food consumption than non-recipients. Food assistance also increased food consumption expenditures but had no significant impact on food purchases and total consumption expenditures. Overall, our findings demonstrate that food assistance can be an effective instrument for improving diets and enhancing the food security of people living with HIV/AIDS. 相似文献
86.
Martijn B. A. van der Wal Wim E. Tuinebreijer Monica C. T. Bloemen Pauline D. H. M. Verhaegen Esther Middelkoop Paul P. M. van Zuijlen 《Quality of life research》2012,21(1):13-23
Purpose
The Patient and Observer Scar Assessment Scale (POSAS) is a questionnaire that was developed to assess scar quality. It consists of two separate six-item scales (Observer Scale and Patient Scale), both of which are scored on a 10-point rating scale. After many years of experience with this scale in burn scar assessment, it is appropriate to examine its psychometric properties using Rasch analysis. 相似文献87.
88.
Marjolein M. N. Leeuwenburgh MD PhD Hein B. A. C. Stockmann MD PhD Wim H. Bouma MD PhD Alexander P. J. Houdijk MD PhD Matthijs F. Verhagen MD Bart Vrouenraets MD PhD Lodewijk P. J. Cobben MD PhD Patrick M. M. Bossuyt PhD Jaap Stoker MD PhD Marja A. Boermeester MD PhD the OPTIMAP Study Group 《Academic emergency medicine》2014,21(5):487-496
89.
Wendy van Dorp Ivana M.M. van der Geest Joop S.E. Laven Wim C.J. Hop Sebastian J.C.M.M. Neggers Andrica C.H. de Vries Rob Pieters Marry M. van den Heuvel-Eibrink 《European journal of cancer (Oxford, England : 1990)》2013,49(6):1280-1286
BackgroundAlthough gonadal toxicity has been reported, no data are available on recovery of gonadal function in very long-term survivors of childhood cancer. Inhibin B is a novel reliable serum marker which has been shown to be of value in childhood cancer survivor studies to identify risk groups for impaired gonadal function, but consecutive long-term follow-up studies using serum inhibin B as a marker are not available.ObjectiveTo evaluate possible recovery of gonadal dysfunction over time in adult male survivors of childhood cancer.MethodsIn this retrospective study, adult male long-term childhood cancer survivors (n = 201) who visited our outpatient late effects clinic were included and we used inhibin B as a surrogate marker for gonadal function.ResultsMedian age at diagnosis was 5.9 years (range 0.0–17.5) and discontinuation of treatment was reached at a median age of 8.2 years (range 0.0–20.8). Inhibin B levels were first measured after a median follow-up time of 15.7 years (range 3.0–37.0). Median interval between the first (T1) and second measurement (T2) was 3.3 years (range 0.7–11.3). Median inhibin B level was 127 ng/L (range 5–366) at T1 and 155 ng/L (range 10–507) at T2. The prediction model suggests that inhibin B levels do not normalise in survivors with a very low Inhibin B level at T1.ConclusionsOur results suggest that recovery of gonadal function is possible even long after discontinuation of treatment. However, this recovery does not seem to occur in survivors who already reached critically low inhibin B levels after discontinuation of treatment. 相似文献
90.
ABSTRACT: BACKGROUND: Research showed that promising approaches such as benchmarking, operations research, lean management and six sigma, could be adopted to improve patient logistics in healthcare. To our knowledge, little research has been conducted to obtain an overview on the use, combination and effects of approaches to improve patient logistics in hospitals. We therefore examined the approaches and tools used to improve patient logistics in Dutch hospitals, the reported effects of these approaches on performance, the applied support structure and the methods used to evaluate the effects. METHODS: A survey among experts on patient logistics in 94 Dutch hospitals. The results were analysed using cross tables. RESULTS: Forty-eight percent of all hospitals participated. Ninety-eight percent reported to have used multiple approaches, 39% of them used five or more approaches. Care pathways were the preferred approach by 43% of the hospitals, followed by business process re-engineering and lean six sigma (both 13%). Flowcharts were the most commonly used tool, they were used on a regular basis by 94% of the hospitals. Less than 10% of the hospitals used data envelopment analysis and critical path analysis on a regular basis. Most hospitals (68%) relied on external support for process analyses and education on patient logistics, only 24% had permanent internal training programs on patient logistics. Approximately 50% of the hospitals that evaluated the effects of approaches on efficiency, throughput times and financial results, reported that they had accomplished their goals. Goal accomplishment in general hospitals ranged from 63% to 67%, in academic teaching hospitals from 0% to 50%, and in teaching hospitals from 25% to 44%. More than 86% performed an evaluation, 53% performed a post-intervention measurement. CONCLUSIONS: Patient logistics appeared to be a rather new subject as most hospitals had not selected a single approach, they relied on external support and they did not have permanent training programs. Hospitals used a combination of approaches and tools, about half of the hospitals reported goal accomplishment and no approach seemed to outperform the others. To make improvement efforts more successful, research should be conducted into the selection and application of approaches, their contingency factors, and goal-setting procedures. 相似文献