| 1. |
- Boxall, A. B. A., et al.
(författare)
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Pharmaceuticals and Personal Care Products in the Environment: What Are the Big Questions?
- 2012
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 120:9, s. 1221-1229
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. OBJECTIVE: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. DATA SOURCES: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. DATA SYNTHESIS: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, a effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. CONCLUSIONS: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.
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| 2. |
- Dakers, A, et al.
(författare)
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Ecosystem Services
- 2002
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Ingår i: Understanding and Solving Environmental Problems in the 21st Century. ; , s. 127-138
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Fortin, G. M., et al.
(författare)
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Glutamate corelease promotes growth and survival of midbrain dopamine neurons
- 2012
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17477-17491
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have proposed that glutamate corelease by mesostriatal dopamine (DA) neurons regulates behavioral activation by psychostimulants.How and when glutamate release by DA neurons might play this role remains unclear. Considering evidence for early expression of the type 2 vesicular glutamate transporter in mesencephalic DA neurons, we hypothesized that this cophenotype is particularly important during development. Using a conditional gene knock-out approach to selectively disrupt the Vglut2 gene in mouse DA neurons, we obtained in vitro and in vivo evidence for reduced growth and survival of mesencephalic DA neurons, associated with a decrease in the density of DA innervation in the nucleus accumbens, reduced activity-dependent DA release, and impaired motor behavior. These findings provide strong evidence for a functional role of the glutamatergic cophenotype in the development of mesencephalic DA neurons, opening new perspectives into the pathophysiology of neurodegenerative disorders involving the mesostriatal DA system.
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| 4. |
- Mai, P., et al.
(författare)
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An analytical framework to understand individual running-related injury risk response patterns to footwear
- 2022
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Ingår i: Proceedings of the Institution of Mechanical Engineers, Part P. - : SAGE Publications. - 1754-3371.
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Tidskriftsartikel (refereegranskat)abstract
- Running footwear is continuously being modified and improved; however, running-related overuse injury rates remain high. Nevertheless, novel manufacturing processes enable the production of individualized running shoes that can fit the individual needs of runners, with the potential to reduce injury risk. For this reason, it is essential to investigate functional groups of runners, a collective of runners who respond similarly to a footwear intervention. Therefore, the objective of this study was to develop a framework to identify functional groups based on their individual footwear response regarding injury-specific running-related risk factors for Achilles tendinopathy, Tibial stress fractures, Medial tibial stress syndrome, and Patellofemoral pain syndrome. In this work, we quantified the footwear response patterns of 73 female and male participants when running in three different footwear conditions using unsupervised learning (k-means clustering). For each functional group, we identified the footwear conditions minimizing the injury-specific risk factors. We described differences in the functional groups regarding their running style, anthropometric, footwear perception, and demographics. The results implied that most functional groups showed a tendency for a single footwear condition to reduce most biomechanical risk factors for a specific overuse injury. Functional groups often differed in their hip and pelvis kinematics as well as their subjective rating of the footwear conditions. The footwear intervention only partially affected biomechanical risk factors attributed to more proximal joints. Due to its adaptive nature, the framework could be applied to other footwear interventions or performance-related biomechanical variables.
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| 5. |
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| 6. |
- Alsiö, Johan, et al.
(författare)
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Enhanced Sucrose and Cocaine Self-Administration and Cue-Induced Drug Seeking after Loss of VGLUT2 in Midbrain Dopamine Neurons in Mice
- 2011
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 31:35, s. 12593-12603
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Tidskriftsartikel (refereegranskat)abstract
- The mesostriatal dopamine (DA) system contributes to several aspects of responses to rewarding substances and is implicated in conditions such as drug addiction and eating disorders. A subset of DA neurons has been shown to express the type 2 Vesicular glutamate transporter (Vglut2) and may therefore corelease glutamate. In the present study, we analyzed mice with a conditional deletion of Vglut2 in DA neurons (Vglut2(f/f;DAT-Cre)) to address the functional significance of the glutamate-DA cophenotype for responses to cocaine and food reinforcement. Biochemical parameters of striatal DA function were also examined by using DA receptor autoradiography, immediate-early gene quantitative in situ hybridization after cocaine challenge, and DA-selective in vivo chronoamperometry. Mice in which Vglut2 expression had been abrogated in DA neurons displayed enhanced operant self-administration of both high-sucrose food and intravenous cocaine. Furthermore, cocaine seeking maintained by drug-paired cues was increased by 76%, showing that reward-dependent plasticity is perturbed in these mice. In addition, several lines of evidence suggest that adaptive changes occurred in both the ventral and dorsal striatum in the absence of VGLUT2: DA receptor binding was increased, and basal mRNA levels of the DA-induced early genes Nur77 and c-fos were elevated as after cocaine induction. Furthermore, in vivo challenge of the DA system by potassium-evoked depolarization revealed less DA release in both striatal areas. This study demonstrates that absence of VGLUT2 in DA neurons leads to perturbations of reward consumption as well as reward-associated memory, features of particular relevance for addictive-like behavior.
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| 7. |
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| 8. |
- Berube-Carriere, Noemie, et al.
(författare)
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Ultrastructural characterization of the mesostriatal dopamine innervation in mice, including two mouse lines of conditional VGLUT2 knockout in dopamine neurons
- 2012
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 35:4, s. 527-538
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Tidskriftsartikel (refereegranskat)abstract
- Despite the increasing use of genetically modified mice to investigate the dopamine (DA) system, little is known about the ultrastructural features of the striatal DA innervation in the mouse. This issue is particularly relevant in view of recent evidence for expression of the vesicular glutamate transporter 2 (VGLUT2) by a subset of mesencephalic DA neurons in mouse as well as rat. We used immuno-electron microscopy to characterize tyrosine hydroxylase (TH)-labeled terminals in the core and shell of nucleus accumbens and the neostriatum of two mouse lines in which the Vglut2 gene was selectively disrupted in DA neurons (cKO), their control littermates, and C57BL/6/J wild-type mice, aged P15 or adult. The three regions were also examined in cKO mice and their controls of both ages after dual THVGLUT2 immunolabeling. Irrespective of the region, age and genotype, the TH-immunoreactive varicosities appeared similar in size, vesicular content, percentage with mitochondria, and exceedingly low frequency of synaptic membrane specialization. No dually labeled axon terminals were found at either age in control or in cKO mice. Unless TH and VGLUT2 are segregated in different axon terminals of the same neurons, these results favor the view that the glutamatergic cophenotype of mesencephalic DA neurons is more important during the early development of these neurons than for the establishment of their scarce synaptic connectivity. They also suggest that, in mouse even more than rat, the mesostriatal DA system operates mainly through non-targeted release of DA, diffuse transmission and the maintenance of an ambient DA level.
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| 9. |
- Cheema, PK, et al.
(författare)
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International variability in the reimbursement of cancer drugs by publically funded drug programs
- 2012
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Ingår i: Current oncology (Toronto, Ont.). - : MDPI AG. - 1718-7729. ; 19:3, s. E165-E176
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Evaluate inter-country variability in the reimbursement of publically funded cancer drugs, and identify factors such as cost containment measures that may contribute to variability. Methods: As of February 28, 2010, licensed indications for 10 cancer drugs (bevacizumab, bortezomib, cetuximab, erlotinib, imatinib, pemetrexed, rituximab, sorafenib, sunitinib, and trastuzumab) were obtained from the drug registries of 6 licensing authorities corresponding to 13 countries or regions: Australia, Canada (Ontario), England, Finland, France, Italy, Germany, Japan, New Zealand, the Netherlands, Scotland, Sweden, and the United States (Medicare Parts B and D). Number of licensed indications reimbursed by public payers and the use of cost containment measures were obtained by survey of health authorities involved in reimbursement and through public documents. Results: The 48 identified licensed indications varied between agencies (range: 36–44 indications). Finland, France, Germany, Sweden, and the United States reimbursed the highest percentage of indications (range: 90%–100%). Canada (54%), Australia (46%), Scotland (40%), England (38%), and New Zealand (25%) reimbursed the least. All 5 countries with the lowest rate of reimbursement incorporated a cost-effectiveness analysis into reimbursement decisions and rejected submissions for reimbursement mainly because of lack of cost effectiveness; in New Zealand, lack of cost effectiveness was the second leading cause of rejection after excessive cost. In 9 countries, risk-sharing agreements were used to contain costs. Indications initially not recommended for reimbursement (9 in Australia, 5 in Canada, and 3 in England, New Zealand, and Scotland) were subsequently approved with risk-sharing agreements or special pricing arrangements. Conclusions: Reimbursement of publically funded cancer drugs varies globally. The cause is multifactorial.
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