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31.
There are increasing policy and market drivers for removing chemicals of concern from manufacturing processes and products. These drivers have centered primarily on developed countries. However, global activities through the United Nations, individual countries, and advocacy organizations are increasing concerns about chemical impacts in developing countries and economies in transition as well. While reducing the use of chemicals of concern is a primary goal, eliminating such substances without thoughtful consideration for their replacements can lead to regrettable substitutions. Against this backdrop there is growing attention to the identification, assessment, and adoption of safer chemicals, as well as product and process design alternatives. Informed substitution is a critical chemical risk management approach, focused on an intentional transition from chemicals of high concern to chemicals and technological processes of lower concern. Alternatives assessment, an interactive, step-defined process, has emerged as a critical approach to support informed substitution. Over the past decade, a number of tools, approaches, and case examples of alternatives assessment and informed substitution have emerged. Policies and practical experience have followed, improving the landscape of alternatives assessment and informed substitution. This article provides an assessment of the state-of-practice of both alternatives assessment and informed substitution methods, policies, and practices. We identify key needs and actions that can be taken by various stakeholder groups moving forward to advance the field. We conclude that there is a critical need for multi-stakeholder, multi-disciplinary collaboration at a global level to build capacity and support networks that can ensure the growth and success of informed substitution efforts in the future. 相似文献
32.
van de Klundert MA Cremer J Kootstra NA Boot HJ Zaaijer HL 《Journal of viral hepatitis》2012,19(2):e34-e40
For phylogenetic comparison of hepatitis B virus (HBV) isolates, often a region of the HBV surface gene is analysed. Because the surface gene completely overlaps the polymerase gene, its evolution is constrained, and it may not be the best choice for genetic comparison of HBV isolates. Analysing serial sample pairs of 33 chronically HBV-infected, untreated patients, with a cumulative follow-up of 184 years, the synonymous and nonsynonymous substitution rates of a part of the overlapping HBV surface and polymerase genes were compared to those of a nonoverlapping part of the HBV core gene. The substitution rate of the HBV core gene was higher (8.15 × 10(-4) vs 4.57 × 10(-4) substitutions/site/year) than that of the surface gene. The difference was mainly due to a significantly lower synonymous substitution rate in the surface gene, with dN/dS ratios of 0.412 in the core gene and 0.986 in the surface gene. Contrary to the core gene, the number of substitutions in the surface gene was higher in low viraemic hosts, who control HBV infection by suppressing replication. The number of substitutions in the core gene correlated more strongly with the duration of follow-up. The overlapping HBV surface and polymerase genes experience strong negative selection, which limits the number of substitutions. Because the HBV core gene reflects the duration of infection more accurately, it is more suitable for the analysis of short-term viral evolution and of hepatitis B transmission chains. 相似文献
33.
Pablo R. Moya PhD Jens R. Wendland MD Liza M. Rubenstein Kiara R. Timpano PhD Gary A. Heiman MD Jay A. Tischfield MD Robert A. King MD Anne M. Andrews PhD Samanda Ramamoorthy PhD Francis J. McMahon MD Dennis L. Murphy MD 《Movement disorders》2013,28(9):1263-1270
To evaluate the hypothesis that functionally over‐expressing alleles of the serotonin transporter (SERT) gene (solute carrier family 6, member 4, SLC6A4) are present in Tourette's disorder (TD), just as we previously observed in obsessive compulsive disorder (OCD), we evaluated TD probands (N = 151) and controls (N = 858). We genotyped the refined SERT‐linked polymorphic region 5‐HTTLPR/rs25531 and the associated rs25532 variant in the SLC6A4 promoter plus the rare coding variant SERT isoleucine‐to‐valine at position 425 (I425V). The higher expressing 5‐HTTLPR/rs25531 LA allele was more prevalent in TD probands than in controls (χ2 = 5.75; P = 0.017; odds ratio [OR], 1.35); and, in a secondary analysis, surprisingly, it was significantly more frequent in probands who had TD alone than in those who had TD plus OCD (Fisher's exact test; P = 0.0006; OR, 2.29). Likewise, the higher expressing LAC haplotype (5‐HTTLPR/rs25531/rs25532) was more frequent in TD probands than in controls (P = 0.024; OR, 1.33) and also in the TD alone group versus the TD plus OCD group (P = 0.0013; OR, 2.14). Furthermore, the rare gain‐of‐function SERT I425V variant was observed in 3 male siblings with TD and/or OCD and in their father. Thus, the cumulative count of SERT I425V becomes 1.57% in OCD/TD spectrum conditions versus 0.15% in controls, with a recalculated, family‐adjusted significance of χ2 = 15.03 (P < 0.0001; OR, 9.0; total worldwide genotyped, 2914). This report provides a unique combination of common and rare variants in one gene in TD, all of which are associated with SERT gain of function. Thus, altered SERT activity represents a potential contributor to serotonergic abnormalities in TD. The present results call for replication in a similarly intensively evaluated sample. © 2013 Movement Disorder Society 相似文献
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35.
Shinobu Imai Kiyohide Fushimi Karolina Andersson Sundell 《Health Policy and Technology》2018,7(2):194-199
Objectives
The generic substitution of medicines has been introduced in Europe since the 1990s to increase price competition and the use of cheaper equivalents. Patent expiry is assumed to be associated with changes in sales patterns, particularly when combined with generic substitution. Other changes have been observed when prescribers obtain new information on drug safety and efficacy of medicines. This article examines to what extent patent expiry and new medical information on efficacy influence the pharmaceutical sales patterns of antihypertensive medicines in Japan and Sweden.Methods
Angiotensin-converting enzyme inhibitors and angiotensin Ⅱ antagonists (ARBs) were selected, since they are widely used in both Japan and Sweden. The two analysed interventions were patent expiry and published information on lower efficacy for two ARBs. Seasonal autoregressive integrated moving average modelling with intervention was used to analyse changes in sales volumes.Results
Patent expiry was not associated with any significant changes in sales patterns. In Sweden, the sales rate of losartan increased following new information on lower efficacy for candesartan and telmisartan (0.77650 DDDs/1,000 inhabitants per day, p?=?0.0068), whereas candesartan sales decreased (-0.50760 DDDs/1000 inhabitants per day, p?=?0.0058). In Japan, the publication of new efficacy information was also associated with a significant decrease in candesartan (?1.21215 DDDs/1000 inhabitants per day, p?=?0.001).Conclusions
We found sales patterns of antihypertensive medicines were to a large extent affected by information on efficacy rather than patent expiry. However, further assessment is needed for other medicine groups and settings. (248 words) 相似文献36.
Facile synthesis of high specific activity 4‐[1‐14C]butyl‐1,2‐diphenylpyrazolidine‐3,5‐dione (phenylbutazone) using nucleophilic substitution 下载免费PDF全文
Anuradha Singh Heldur Hakk Sara J. Lupton 《Journal of labelled compounds & radiopharmaceuticals》2018,61(4):386-390
Metabolism, environmental fate, and low concentration food residue studies would be facilitated by the use of radiolabeled test articles that can be readily quantified within complex matrices. However, radiochemical approaches for such studies require high specific activities to allow analytical detection of correspondingly low masses of test article. The synthesis of high specific activity (>50 μCi/μmol) [14C]‐radiolabeled phenylbutazone presents a challenge using existing methodology, mainly due to the low solvent volumes required and vigorous refluxing needed to close the pyrazolidinedione ring. Herein, we report on the significant modification of an existing method that allows the synthesis of low masses of high specific activity (>50 μCi/μmol) [14C]‐phenylbutazone under mild conditions with simple purification and high yield. The closure of the pyrazolidinedione ring of 1,2‐diphenyl‐3,5‐pyrazolidinedione was accomplished as a first step with unlabeled 1,2‐diphenylhydrazine and diethyl malonate in 32% yield under gram‐scale conditions, which avoided the challenges of low solvent use and vigorous refluxing. Low mass of high specific activity n‐[1‐14C]‐butyl bromide was then added via a nucleophilic substitution reaction as a final step. Yields ranged from 65% to 92% during multiple synthetic attempts with unlabeled butyl bromide and were greatly influenced by reaction stoichiometry and the selection of base. 相似文献
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38.
《The International journal on drug policy》2014,25(1):53-60
ObjectiveIn 2010 the international HIV/AIDS community called on countries to take action to prevent HIV transmission among people who inject drugs (PWID). To set a baseline we proposed an “accountability matrix”, focusing upon six countries accounting for half of the global population of PWID: China, Malaysia, Russia, Ukraine, Vietnam and the USA. Two years on, we review progress.DesignWe searched peer-reviewed literature, conducted online searches, and contacted experts for ‘grey’ literature. We limited searches to documents published since December 2009 and used decision rules endorsed in earlier reviews.ResultsPolicy shifts are increasing coverage of key interventions for PWID in China, Malaysia, Vietnam and Ukraine. Increases in PWID receiving antiretroviral treatment (ART) and opioid substitution treatment (OST) in both Vietnam and China, and a shift in Malaysia from a punitive law enforcement approach to evidence-based treatment are promising developments. The USA and Russia have had no advances on PWID access to needle and syringe programmes (NSP), OST or ART. There have also been policy setbacks in these countries, with Russia reaffirming its stance against OST and closing down access to information on methadone, and the USA reinstituting its Congressional ban on Federal funding for NSPs.ConclusionsPrevention of HIV infection and access to HIV treatment for PWID is possible. Whether countries with concentrated epidemics among PWID will meet goals of achieving universal access and eliminating new HIV infections remains unknown. As long as law enforcement responses counter public health responses, health-seeking behaviour and health service delivery will be limited. 相似文献
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