| 1. |
- Hjorth, Peder, et al.
(författare)
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Adaptive Water Management : On the Need for Using the Post-WWII Science in Water Governance
- 2023
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Ingår i: Water Resources Management. - : Springer Science and Business Media LLC. - 0920-4741 .- 1573-1650. ; 37:6-7, s. 2247-2270
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Tidskriftsartikel (refereegranskat)abstract
- Although the UN concluded, already in 1997, that water would be the most contentious issue of the 21st century, water governance is still confused, nearly everywhere. Even the severe impacts of escalating water bankruptcy and global warming have so far failed to incur a marked improvement in governance systems. The global community has adopted sustainable development as a common vision and guide for the future. Yet, the adoption of the underlying principles of sustainable development has been slow in the water sector and elsewhere. Despite the realization that water governance is a political issue, the near-universal neoliberal agenda tends to only employ technologic and economic solutions to address water problems. This paper presents a historical overview, from the end of the Second World War (WWII) and onwards, of events that could, or should, have had an impact on water management frameworks. It evidences some important consequences of the institutional rigidity exposed during that period. The paper also turns to the fields of science, policy, and management, to pinpoint failures in the translation of political rhetoric as well as new scientific findings into change at the operational level. It explores how an updated knowledge base could serve a quest for sustainable water governance strategies. It is argued that a persistent failure to learn is an important reason behind the dire state that we are now in. As a result, water management is still based on century-old, technocratic, and instrumental methodologies that fail to take advantage of important scientific advancements since WWII and remain unable to properly deal with real-world complexities and uncertainties. The paper concludes that when it is linked to a transformation of the institutional superstructure, adaptive water management (AWM), a framework rooted in systems thinking, emerges as a prominent way to embark on a needed, radical transformation of the water governance systems.
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| 2. |
- Holm-Waters, Susanna, et al.
(författare)
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Preclinical Pharmacology of 2-(3-Fluoro-5-Methanesulfonyl-phenoxy)Ethyl (Propyl)amine (IRL790), a Novel Dopamine Transmission Modulator for the Treatment of Motor and Psychiatric Complications in Parkinson Disease
- 2020
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0022-3565 .- 1521-0103. ; 374:1, s. 113-125
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Tidskriftsartikel (refereegranskat)abstract
- IRL790 ([2-(3-fluoro-5-methanesulfonylphenoxy)ethyl](propyl)amine, mesdopetam) is a novel compound in development for the clinical management of motor and psychiatric disabilities in Parkinson disease. The discovery of IRL790 was made applying a systems pharmacology approach based on in vivo response profiling. The chemical design idea was to develop a new type of DA D3/D2 receptor type antagonist built on agonist rather than antagonist structural motifs. We hypothesized that such a dopamine antagonist with physicochemical properties similar to agonists would exert antidyskinetic and antipsychotic effects in states of dysregulated dopaminergic signaling while having little negative impact on physiologic dopamine transmission and, hence, minimal liability for side effects related to dopamine-dependent functions. At the level of in vivo pharmacology, IRL790 displays balancing effects on aberrant motor phenotypes, reducing L-DOPA-induced dyskinesias in the rodent 6-hydroxydopamine lesion model and reducing psychostimulant-induced locomotor hyperactivity elicited by pretreatment with either d-amphetamine or dizocilpine, without negatively impacting normal motor performance. Thus, IRL790 has the ability to normalize the behavioral phenotype in hyperdopaminergic as well as hypoglutamatergic states. Neurochemical and immediate early gene (IEG) response profiles suggest modulation of DA neurotransmission, with some features, such as increased DA metabolites and extracellular DA, shared by atypical antipsychotics and others, such as increased frontal cortex IEGs, unique to IRL790. IRL790 also increases extracellular levels of acetylcholine in the prefrontal cortex and ventral hippocampus. At the receptor level, IRL790 appears to act as a preferential DA D3 receptor antagonist. Computational docking studies support preferential affinity at D3 receptors with an agonist-like binding mode. SIGNIFICANCE STATEMENT This paper reports preclinical pharmacology along with molecular modeling results on IRL790, a novel compound in clinical development for the treatment of motor and psychiatric complications in advanced Parkinson disease. IRL790 is active in models of perturbed dopaminergic and glutamatergic signaling, including rodent 6-hydroxydopamine L-DOPA-induced dyskinesias and psychostimulant-induced hyperactivity, in a dose range that does not impair normal behavior. This effect profile is attributed to interactions at dopamine D2/D3 receptors, with a 6- to 8-fold preference for the D3 subtype.
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| 3. |
- Stan, Tiberiu Loredan, et al.
(författare)
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Neurophysiological treatment effects of mesdopetam, pimavanserin and clozapine in a rodent model of Parkinson's disease psychosis
- 2024
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Ingår i: Neurotherapeutics. - : Elsevier. - 1878-7479 .- 1933-7213. ; 21:2, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Psychosis in Parkinson's disease is a common phenomenon associated with poor outcomes. To clarify the pathophysiology of this condition and the mechanisms of antipsychotic treatments, we have here characterized the neurophysiological brain states induced by clozapine, pimavanserin, and the novel prospective antipsychotic mesdopetam in a rodent model of Parkinson's disease psychosis, based on chronic dopaminergic denervation by 6-OHDA lesions, levodopa priming, and the acute administration of an NMDA antagonist. Parallel recordings of local field potentials from eleven cortical and sub-cortical regions revealed shared neurophysiological treatment effects for the three compounds, despite their different pharmacological profiles, involving reversal of features associated with the psychotomimetic state, such as a reduction of aberrant high-frequency oscillations in prefrontal structures together with a decrease of abnormal synchronization between different brain regions. Other drug-induced neurophysiological features were more specific to each treatment, affecting network oscillation frequencies and entropy, pointing to discrete differences in mechanisms of action. These findings indicate that neurophysiological characterization of brain states is particularly informative when evaluating therapeutic mechanisms in conditions involving symptoms that are difficult to assess in rodents such as psychosis, and that mesdopetam should be further explored as a potential novel antipsychotic treatment option for Parkinson psychosis.
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| 4. |
- Tussupova, Kamshat, et al.
(författare)
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Drying lakes : A review on the applied restoration strategies and health conditions in contiguous areas
- 2020
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Ingår i: Water. - : MDPI AG. - 2073-4441. ; 12:3
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Forskningsöversikt (refereegranskat)abstract
- Decrease of saline lakes, which comprise 44% of all available lake water, is a major concern. It additionally accelerates the desertification process of the region. Thus, various countries have taken different actions in protecting their lake water levels. The aim of this paper is to assess different strategies directed to tackle the decreased lake water levels in Lake Urmia and the Aral Sea, which split into the North Aral Sea and South Aral Sea. These are among the world's largest and fastest drying saline lakes observed in the past 50 years and have both reduced to 10% of their original size. The paper presents a thorough review of academic reports, official documents, and databases. Although the dry-up of a lake is a natural process, it has been sped up by human interventions in the hydrological cycle. Dust storms (strong winds) cause problems in the surroundings. In the case of the Aral Sea, they transmit the pollutants from the dry lake bed causing severe health issues. Various strategies were implemented to manage the socio-economic conditions caused due to the drying of lakes. The strategy implemented for the North Aral Sea was to restore the lake by reducing the water withdrawals from the Syr Darya river, which lead to increased water inflow to the sea. The suggested strategy for Lake Urmia was to restore the lake by water transfer activities from various water sources. These projects have not yet been realized. The strategy implemented for the South Aral Sea was to use a dry lake bed to diversify the economy by oil and mineral extraction along with developing a tourist industry based on the considerable interest to come and observe an ecological disaster of such monumental proportions. These findings show that there is no common best solution for this type of problem. The best fit depends on the local context and it is strongly path-dependent.
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