Appropriate modelling of climate change impacts on river flooding

Global climate change is likely to increase temperatures, change precipitation patterns\ud and probably raise the frequency of extreme events. Impacts of climate change on river\ud flooding may be considerable and may cause enormous economical, social and\ud environmental damage and even loss of lives. This necessitates the application of robust\ud and accurate flood estimation procedures to provide a strong basis for investments in\ud flood protection measures with climate change.\ud A broad palette of models is available to fulfil this requirement. More complex models\ud generally have larger data requirements and computational costs, but may result in\ud smaller model output uncertainties and associated costs. It would seem that an optimum\ud complexity associated with minimum total costs or uncertainty exists. This raises the\ud question what such an appropriate model should look like given the specific modelling\ud objective and research area. Or which physical processes and data should be\ud incorporated and which mathematical process formulations should be used at which\ud spatial and temporal scale, to obtain an appropriate model level?\ud Therefore, the main objectives of this study are the determination of the appropriate\ud model complexity dependent on modelling objective and research area and the\ud assessment of the climate change impact on river flooding with an appropriate model.\ud The Meuse basin in Belgium and France serves as an application area in this thesis. The\ud first objective is dealt with in chapter 2, 3, 4 and 5 and constitutes the main part of this\ud thesis. The second objective is mainly treated in chapter 4 and 6

Clinical Applications of [¹²³I]FP-CIT SPECT Imaging

Dopamine transporter (DAT) imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT) is commonly used in routine clinical studies to exclude or detect a loss of striatal DATs in individual patients with a movement disorder or dementia. In this chapter, we describe the clinical applications of [123I]FP-CIT SPECT imaging. To facilitate the interpretation of [123I]FP-CIT SPECT images, we first describe the results of [123I]FP-CIT SPECT studies in healthy controls. Thereafter, we describe the typical findings when applying this technique in movement disorders and dementia characterised by a loss of striatal DATs (e.g. Parkinson's disease and dementia with Lewy bodies). We will also describe the possibilities to analyse [123I]FP-CIT SPECT scans in the setting of routine clinical practice. Finally, we briefly discuss the characterisation of extrastriatal [123I]FP-CIT binding and its potential role in future studies.</p

Clinical Applications of [¹²³I]FP-CIT SPECT Imaging

Dopamine transporter (DAT) imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT) is commonly used in routine clinical studies to exclude or detect a loss of striatal DATs in individual patients with a movement disorder or dementia. In this chapter, we describe the clinical applications of [123I]FP-CIT SPECT imaging. To facilitate the interpretation of [123I]FP-CIT SPECT images, we first describe the results of [123I]FP-CIT SPECT studies in healthy controls. Thereafter, we describe the typical findings when applying this technique in movement disorders and dementia characterised by a loss of striatal DATs (e.g. Parkinson's disease and dementia with Lewy bodies). We will also describe the possibilities to analyse [123I]FP-CIT SPECT scans in the setting of routine clinical practice. Finally, we briefly discuss the characterisation of extrastriatal [123I]FP-CIT binding and its potential role in future studies.</p

The Effect of Escitalopram on Central Serotonergic and Dopaminergic Systems in Patients with Cervical Dystonia, and Its Relationship with Clinical Treatment Effects:A Double-Blind Placebo-Controlled Trial

Purpose:The pathophysiology of cervical dystonia (CD) is thought to be related to changes in dopamine and serotonin levels in the brain. We performed a double-blind trial with escitalopram (selective serotonin reuptake inhibitor; SSRI) in patients with CD. Here, we report on changes in dopamine D(2/3)receptor (D2/3R), dopamine transporter (DAT) and serotonin transporter (SERT) binding potential (BPND) after a six-week treatment course with escitalopram or placebo.Methods:CD patients had [123I]FP-CIT SPECT (I-123 fluoropropyl carbomethoxy-3 beta-(4-iodophenyltropane) single-photon emission computed tomography) scans, to quantify extrastriatal SERT and striatal DAT, and [123I]IBZM SPECT (I-123 iodobenzamide SPECT) scans to quantify striatal D2/3R BPND before and after six weeks of treatment with either escitalopram or placebo. Treatment effect was evaluated with the Clinical Global Impression scale for dystonia, jerks and psychiatric symptoms, both by physicians and patients.Results:In both patients treated with escitalopram and placebo there were no significant differences after treatment in SERT, DAT or D2/3R BPND. Comparing scans after treatment with escitalopram (n = 8) to placebo (n = 8) showed a trend (p= 0.13) towards lower extrastriatal SERT BPND in the SSRI group (median SERT occupancy of 64.6%). After treatment with escitalopram, patients who reported a positive effect on dystonia or psychiatric symptoms had significantly higher SERT occupancy compared to patients who did not experience an effect.Conclusion:Higher extrastriatal SERT occupancy after treatment with escitalopram is associated with a trend towards a positive subjective effect on dystonia and psychiatric symptoms in CD patients

Activation of sp3-CH Bonds in a Mono(pentamethylcyclopentadienyl)yttrium Complex. X-ray Crystal Structures and Dynamic Behavior of Cp*Y(o-C6H4CH2NMe2)2 and Cp*Y[o-C6H4CH2NMe(CH2-μ)][μ-o-C6H4CH2NMe(CH2-μ)]YCp*[THF]

Reaction of Y(o-C6H4CH2NMe2)3 (1) with Cp*H gives Cp*Y(o-C6H4CH2NMe2)2 (2), which crystallizes in the monoclinic space group P21/n (No. 14) with a = 18.607 (4) Å, b = 15.633 (3) Å, c = 8.861 (3) Å, β = 102.73 (3)°, and Z = 4. Least-squares refinement with 3006 independent reflections (F > 4.0σ(F)) led to a final RF (wR) of 0.053 (0.068). The molecular structure consists of monomeric Cp*Y(o-C6H4CH2NMe2)2 units with a regularly bonded Cp* ligand (Y-Ct = 2.367 (3) Å), equal Y-C(aryl) distances (2.479 (6) and 2.471 (6) Å), and both nitrogen atoms coordinated to yttrium (Y-N distances = 2.568 (5) and 2.506 (6) Å). Short intramolecular Y···H distances (Y···H(181) = 3.00 (6) Å, Y···H(183) = 3.13 (9) Å) indicate agostic interactions. The long N(2)-C(18) bond (1.55 (1) Å) and the short Y···C(18) distance (3.202 (8) Å) indicate an Y···C-N agostic interaction. Thermolysis of 2 in THF gives Cp*Y[o-C6H4CH2NMe(CH2-μ)][μ-o-C6H4CH2NMe(CH2-μ)]YCp*[THF] (3) and N,N-dimethylbenzylamine. Compound 3 crystallizes in the monoclinic space group P21/c (No. 14) with a = 17.004 (1) Å, b = 13.962 (1) Å, c = 20.129 (3) Å, β = 92.94 (1)°, and Z = 4. Least-squares refinement with 4578 independent reflections (F > 5.0σ(F)) led to a final RF (wR) of 0.065 (0.070). The molecule consists of two Cp*Y fragments (Y(1)-Ct(1) = 2.420 (6) Å, Y(2)-Ct(2) = 2.414 (5) Å), bridged by two methylene carbon atoms (Y(1)-C(9) = 2.591 (10) Å, Y(2)-C(9) = 2.527 (9) Å, Y(1)-C(18) = 2.622 (10) Å, Y(2)-C(18) = 2.532 (10) Å) and one aryl carbon atom (Y(1)-C(1) = 2.702 (8) Å, Y(2)-C(1) = 2.547 (9) Å). The remaining aryl group is not bridging (Y(1)-C(10) = 2.441 (8) Å). Asymmetry in 3 is caused by THF coordination (Y(2)-O = 2.446 (5) Å). Thermolysis of 2 can be explained by dissociation of an Y-N dative bond followed by activation of an agostic C-H bond

Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer's disease: a cohort study

Objectives: Dementia with Lewy bodies (DLB) accounts for 10%-15% of dementia cases at autopsy and has distinct clinical features associated with earlier institutionalisation and a higher level of carer distress than are seen in Alzheimer's disease (AD). At present, there is on-going debate as to whether DLB is associated with a more rapid cognitive decline than AD. An understanding of the rate of decline of cognitive and non-cognitive symptoms in DLB may help patients and carers to plan for the future. Design: In this cohort study, the authors compared 100 AD and 58 DLB subjects at baseline and at 12-month follow-up on cognitive and neuropsychiatric measures. Setting: Patients were recruited from 40 European centres. Participants: Subjects with mild-moderate dementia. Diagnosis of DLB or AD required agreement between consensus panel clinical diagnosis and visual rating of 123I-FP-CIT (dopamine transporter) single photon emission computed tomography neuroimaging. Outcome measures: The Cambridge Cognitive Examination including Mini-Mental State Examination and Neuropsychiatric Inventory (NPI). Results: The AD and DLB groups did not differ at baseline in terms of age, gender, Clinical Dementia Rating score and use of cholinesterase inhibitors or memantine. NPI and NPI carer distress scores were statistically significantly higher for DLB subjects at baseline and at follow-up, and there were no differences between AD and DLB in cognitive scores at baseline or at follow-up. There was no significant difference in rate of progression of any of the variables analysed. Conclusions: DLB subjects had more neuropsychiatric features at baseline and at follow-up than AD, but the authors did not find any statistically significant difference in rate of progression between the mild-moderate AD and DLB groups on cognitive or neuropsychiatric measures over a 12-month follow-up perio