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

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

The role of preclinical SPECT in oncological and neurological research in combination with either CT or MRI

Preclinical imaging with SPECT combined with CT or MRI is used more and more frequently and has proven to be very useful in translational research. In this article, an overview of current preclinical research applications and trends of SPECT combined with CT or MRI, mainly in tumour imaging and neuroscience imaging, is given and the advan- tages and disadvantages of the different approaches are de- scribed. Today SPECT and CT systems are often integrated into a single device (commonly called a SPECT/CT system), whereas at present combined SPECT and MRI is almost always carried out with separate systems and fiducial markers to combine the separately acquired images. While preclinical SPECT/CT is most widely applied in oncology research, SPECT combined with MRI (SPECT/MRI when integrated in one system) offers the potential for both neuroscience applications and oncological applications. Today CT and MRI are still mainly used to localize radiotracer binding and to improve SPECT quantification, although both CT and MRI have additional potential. Future technology developments may include fast sequential or simultaneous acquisition of (dynamic) multimodality data, spectroscopy, fMRI along with high-resolution anatomic MRI, advanced CT procedures, and combinations of more than two modalities such as combina- tions of SPECT, PET, MRI and CT all together. This will all strongly depend on new technologies. With further advances in biology and chemistry for imaging molecular targets and (patho)physiological processes in vivo, the introduction of new imaging procedures and promising new radiopharmaceu- ticals in clinical practice may be accelerated

Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 Oxidoreductase deficiency

Context: P450 oxidoreductase (POR) is a crucial electron donor to all microsomal P450 cytochrome (CYP) enzymes including 17α-hydroxylase (CYP17A1), 21-hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal hyperplasia with combined glucocorticoid and sex steroid deficiency. P450 oxidoreductase deficiency (ORD) commonly presents neonatally, with disordered sex development in both sexes, skeletal malformations, and glucocorticoid deficiency. \ud \ud Objective: The aim of the study was to describe the clinical and biochemical characteristics of ORD during puberty. \ud \ud Design: Clinical, biochemical, and genetic assessment of seven ORD patients (five females, two males) presenting during puberty was conducted. \ud \ud Results: Predominant findings in females were incomplete pubertal development (four of five) and large ovarian cysts (five of five) prone to spontaneous rupture, in some only resolving after combined treatment with estrogen/progestin, GnRH superagonists, and glucocorticoids. Pubertal development in the two boys was more mildly affected, with some spontaneous progression. Urinary steroid profiling revealed combined CYP17A1 and CYP21A2 deficiencies indicative of ORD in all patients; all but one failed to mount an appropriate cortisol response to ACTH stimulation indicative of adrenal insufficiency. Diagnosis of ORD was confirmed by direct sequencing, demonstrating disease-causing POR mutations. \ud \ud Conclusion: Delayed and disordered puberty can be the first sign leading to a diagnosis of ORD. Appropriate testosterone production during puberty in affected boys but manifest primary hypogonadism in girls with ORD may indicate that testicular steroidogenesis is less dependent on POR than adrenal and ovarian steroidogenesis. Ovarian cysts in pubertal girls may be driven not only by high gonadotropins but possibly also by impaired CYP51A1-mediated production of meiosis-activating sterols due to mutant POR

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

Relationships between Serotonin Transporter Binding in the Raphe Nuclei, Basal Ganglia, and Hippocampus with Clinical Symptoms in Cervical Dystonia:A [C]DASB Positron Emission Tomography Study

PurposeAlterations of the central serotonergic system have been implicated in the pathophysiology of dystonia. In this molecular imaging study, we assessed whether altered presynaptic serotonin transporter (SERT) binding contributes to the pathophysiology of cervical dystonia (CD), concerning both motor and non-motor symptoms (NMS).MethodsWe assessed the non-displaceable binding potential (BPND) using the selective SERT tracer [11C]DASB and positron emission tomography (PET) in 14 CD patients and 12 age- and gender-matched controls. Severity of motor symptoms was scored using the Toronto Western Spasmodic Torticollis Rating Scale and Clinical Global Impression jerks/tremor scale. NMS for depressive symptoms, anxiety, fatigue, and sleep disturbances were assessed with quantitative rating scales. The relationship between SERT binding and clinical patient characteristics was analyzed with the Spearman’s rho test and multiple regression.ResultsWhen comparing the CD patients with controls, no significant differences in BPND were found. Higher BPND in the dorsal raphe nucleus was statistically significantly correlated (p &lt; 0.001) with motor symptom severity (rs = 0.65), pain (rs = 0.73), and sleep disturbances (rs = 0.73), with motor symptom severity being the most important predictor of SERT binding. Furthermore, fatigue was negatively associated with the BPND in the medial raphe nucleus (rs = −0.61, p = 0.045), and sleep disorders were positively associated with the BPND in the caudate nucleus (rs = 0.58, p = 0.03) and the hippocampus (rs = 0.56, p = 0.02).ConclusionMotor symptoms, as well as pain, sleep disturbances, and fatigue in CD showed a significant relationship with SERT binding in the raphe nuclei. Moreover, fatigue showed a significant relationship with the medial raphe nucleus and sleep disorders with the caudate nucleus and hippocampus. These findings suggest that an altered serotonergic signaling in different brain areas in CD is related to different motor as well as NMS, which will further stimulate research on the role of serotonin in the pathogenesis of dystonia

Early-stage [123I]beta-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson's disease

beta-CIT binding in both caudate nuclei was lower than in the group of patients with IPD. In addition, putamen to caudate binding ratios were higher in the group of APS patients. In spite of these differences, individual binding values showed considerable overlap between the groups. CONCLUSION: [(123)I]beta-CIT SPECT scanning in early-stage, untreated parkinsonian patients revealed a relative sparing of the caudate nucleus in patients with IPD as compared to patients later (re)diagnosed with APS. Nevertheless, the pattern of striatal involvement appears to have little predictive value for a later re-diagnosis of APS in individual case