Climate Change and Causation:Joining Law and Climate Science on the basis of Formal Logic

A strict application of legal tests to find the cause of an event has always been a challenge for a coherent causal analysis. This is again the case for making causal statements in the climate change context, although we are witnessing unprecedented impacts of a changing climate at a global scale. While probabilistic event attribution provides information linking greenhouse gas emission levels to observable characteristics of extreme weather and climate related events, the conventional understanding of causation in law provides a very limited response to this scientific knowledge. We offer a new matrix for developing causal explanations based on formal logic, for a coherent analysis that is compatible with climate science and law. This matrix causally explains the relation between emissions, the increase in global mean surface temperature, the general increase in frequency and severity of climate related events and, most significantly, between emissions and individual climate related events

Current Progress in CNS Imaging of Myotonic Dystrophy

Neuroimaging in myotonic dystrophies provided a major contribution to the insight into brain involvement which is highly prevalent in these multisystemic disorders. Particular in Myotonic Dystrophy Type 1, conventional MRI first revealed hyperintense white matter lesions, predominantly localized in the anterior temporal lobe. Brain atrophy and ventricle enlargement were additional early findings already described almost 30 years ago. Since then, more advanced and sophisticated imaging methods have been applied in Myotonic Dystrophy Types 1 and 2. Involvement of actually normal appearing white matter and widespread cortical affection in PET studies were key results toward the recognition of diffuse and not only focally localized brain pathology in vivo. Later, structural abnormalities of both, gray and white matter, have been found in both forms of the disorder, albeit more prominent in myotonic dystrophy type 1. In Type 1, a consistent widespread cortical and subcortical involvement of gray and white matter affecting all lobes, brainstem and cerebellum was observed. Spectroscopy studies gave additional evidence of neuronal and glial damage in both types. Central questions regarding the origin and spatiotemporal evolution of the CNS involvement and its relevance for clinical symptoms had already been raised 30 years ago, however are still not answered. Results of correlation analyses between neuroimaging and clinical parameters are diverse and with few exceptions not well reproducible across studies. It may be related to the fact that most of the reported studies included only small numbers of subjects, sometimes even not separating Myotonic Dystrophy Type 1 from Type 2. But this heterogeneity may also support the current point of view that the clinical impairments are not simply linked to specific and regionally circumscribed structural or functional brain alterations. It seems more convincing that disturbed networks build the functional and structural substrate of clinical symptoms in these disorders as it is proposed in other neuropsychiatric diseases. Consecutively, structural and functional network analyses may provide additional information regarding the link between brain pathology and clinical symptoms. Up to now, only cross-sectional neuroimaging studies have been published. To analyze the temporal evolution of brain affection, longitudinal studies are urgently needed, and systematic natural history data would be useful to identify potential biomarkers for therapeutic studies

Neuropsychological Features of Patients with Spinocerebellar Ataxia (SCA) Types 1, 2, 3, and 6

A subtype-specific impairment of cognitive functions in spinocerebellar ataxia (SCA) patients is still debated. Thirty-two SCA patients (SCA1, 6; SC2, 3; SCA3, 15; SCA6, 8) and 14 matched healthy controls underwent neuropsychological evaluation testing attention, executive functions, episodic and semantic memory, and motor coordination. Severity of ataxia was assessed with the Scale for the Assessment and Rating of Ataxia (SARA), nonataxia symptoms with the Inventory of Non-Ataxia Symptoms. Depressive symptoms were evaluated with the Beck Depression Inventory. The SARA scores of our SCA patients (range 1–19.5) indicated an overall moderate ataxia, most pronounced in SCA6 and SCA1. Mean number of nonataxia symptoms (range 0–2.2) were most distinct in SCA1 and nearly absent in SCA6. SCA1 performed poorer than controls in 33% of all cognitive test parameters, followed by SCA2, SCA3, and SCA6 patients (17%). SCA 1–3 patients presented mainly attentional and executive dysfunctions while semantic and episodic memory functions were preserved. Attentional and executive functions were partly correlated with ataxia severity and fine motor coordination. All patients exhibited mildly depressed mood. Motor and dominant hand functions were more predictive for depressed mood than cognitive measures or overall ataxia. Besides motor impairments in all patients, SCA patients with extracerebellar pathology (SCA 1–3) were characterized by poor frontal attentional and executive dysfunction while mild cognitive impairments in predominantly cerebellar SCA6 patients appeared to reflect mainly cerebellar dysfunction. Regarding the everyday relevance of symptoms, (dominant) motor hand functioning emerged as a marker for the patient’s mood

Derivation of Fiber Orientations From Oblique Views Through Human Brain Sections in 3D-Polarized Light Imaging

3D-Polarized Light Imaging (3D-PLI) enables high-resolution three-dimensional mapping of the nerve fiber architecture in unstained histological brain sections based on the intrinsic birefringence of myelinated nerve fibers. The interpretation of the measured birefringent signals comes with conjointly measured information about the local fiber birefringence strength and the fiber orientation. In this study, we present a novel approach to disentangle both parameters from each other based on a weighted least squares routine (ROFL) applied to oblique polarimetric 3D-PLI measurements. This approach was compared to a previously described analytical method on simulated and experimental data obtained from a post mortem human brain. Analysis of the simulations revealed in case of ROFL a distinctly increased level of confidence to determine steep and flat fiber orientations with respect to the brain sectioning plane. Based on analysis of histological sections of a human brain dataset, it was demonstrated that ROFL provides a coherent characterization of cortical, subcortical, and white matter regions in terms of fiber orientation and birefringence strength, within and across sections. Oblique measurements combined with ROFL analysis opens up new ways to determine physical brain tissue properties by means of 3D-PLI microscopy

Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich\u27s ataxia

Spinocerebellar ataxia type 3, spinocerebellar ataxia type 6 and Friedreich\u27s ataxia are common hereditary ataxias. Different patterns of atrophy of the cerebellar cortex are well known. Data on cerebellar nuclei are sparse. Whereas cerebellar nuclei have long been thought to be preserved in spinocerebellar ataxia type 6, histology shows marked atrophy of the nuclei in Friedreich\u27s ataxia and spinocerebellar ataxia type 3. In the present study susceptibility weighted imaging was used to assess atrophy of the cerebellar nuclei in patients with spinocerebellar ataxia type 6 (n = 12, age range 41-76 years, five female), Friedreich\u27s ataxia (n = 12, age range 21-55 years, seven female), spinocerebellar ataxia type 3 (n = 10, age range 34-67 years, three female), and age-and gender-matched controls (total n = 23, age range 22-75 years, 10 female). T1-weighted magnetic resonance images were used to calculate the volume of the cerebellum. In addition, ultra-high field functional magnetic resonance imaging was performed with optimized normalization methods to assess function of the cerebellar cortex and nuclei during simple hand movements. As expected, the volume of the cerebellum was markedly reduced in spinocerebellar ataxia type 6, preserved in Friedreich\u27s ataxia, and mildy reduced in spinocerebellar ataxia type 3. The volume of the cerebellar nuclei was reduced in the three patient groups compared to matched controls (P-values \u3c 0.05; two-sample t-tests). Atrophy of the cerebellar nuclei was most pronounced in spinocerebellar ataxia type 6. On a functional level, hand-movement-related cerebellar activation was altered in all three disorders. Within the cerebellar cortex, functional magnetic resonance imaging signal was significantly reduced in spinocerebellar ataxia type 6 and Friedreich\u27s ataxia compared to matched controls (P-values \u3c 0.001, bootstrap-corrected cluster-size threshold; two-sample t-tests). The difference missed significance in spinocerebellar ataxia type 3. Within the cerebellar nuclei, reductions were significant when comparing spinocerebellar ataxia type 6 and Friedreich\u27s ataxia to matched controls (P \u3c 0.01, bootstrap-corrected cluster-size threshold; two-sample t-tests). Susceptibility weighted imaging allowed depiction of atrophy of the cerebellar nuclei in patients with Friedreich\u27s ataxia and spinocerebellar ataxia type 3. In spinocerebellar ataxia type 6, pathology was not restricted to the cerebellar cortex but also involved the cerebellar nuclei. Functional magnetic resonance imaging data, on the other hand, revealed that pathology in Friedreich\u27s ataxia and spinocerebellar ataxia type 3 is not restricted to the cerebellar nuclei. There was functional involvement of the cerebellar cortex despite no or little structural changes

The feasibility of associate EU citizenship for UK citizens post-Brexit

Modern code-conforming buildings have a high probability of surviving major seismic events without collapse, hence minimizing the number of casualties. Nevertheless, the risk of substantial post-earthquake economic losses remains high, as a consequence of inadequate damage prevention guidelines in current earthquake design codes. Rocking post-tensioned moment-resisting frames present a viable damage-free structural solution, with a nominal increase in building costs compared with conventional buildings. This structural system comprises of: (i) unbonded post-tensioned strands to provide overturning resistance and self-centering capability, and (ii) opening joints at the column-foundation and beam-column interfaces designed to rock during a seismic event. Rocking frames with various forms of supplemental damping have been previously examined numerically, adopting different finite element frameworks. However, there is a shortage of numerical studies studying the non-linear dynamic response of pure rocking multi-story post-tensioned moment frames, exclusive of supplementary energy-dissipation elements and devices. Hence, it is critical to develop modelling procedures for multiple stories which adequately capture the full range of their nonlinear dynamic behavior due to the joint rocking mechanism, and investigate the resulting response. Numerical studies are presented herein, including static and dynamic analyses of three- to nine-story building models. The proposed modelling methods are shown to effectively predict the non-linear response of multi-story rocking frames over a wide range of forcing frequencies and amplitudes. It is further concluded that the structural response is influenced by both sub-harmonic resonances and beam-column interactions.</p

Neurochemical Differences in Spinocerebellar Ataxia Type 14 and 1

Autosomal-dominant spinocerebellar ataxias (SCA) are neurodegenerative diseases characterized by progressive ataxia. Here, we report on neurometabolic alterations in spinocerebellar ataxia type 1 (SCA1; SCA-ATXN1) and 14 (SCA14; SCA-PRKCG) assessed by non-invasive 1H magnetic resonance spectroscopy. Three Tesla 1H magnetic resonance spectroscopy was performed in 17 SCA14, 14 SCA1 patients, and in 31 healthy volunteers. We assessed metabolites in the cerebellar vermis, right cerebellar hemisphere, pons, prefrontal, and motor cortex. Additionally, clinical characteristics were obtained for each patient to correlate them with metabolites. In SCA14, metabolic changes were restricted to the cerebellar vermis compared with widespread neurochemical alterations in SCA1. In SCA14, total N-acetylaspartate (tNAA) was reduced in the vermis by 34%. In SCA1, tNAA was reduced in the vermis (24%), cerebellar hemisphere (26%), and pons (25%). SCA14 patients showed 24% lower glutamate+glutamine (Glx) and 46% lower γ-aminobutyric acid (GABA) in the vermis, while SCA1 patients showed no alterations in Glx and GABA. SCA1 revealed a decrease of aspartate (Asp) in the vermis (62%) and an elevation in the prefrontal cortex (130%) as well as an elevation of myo-inositol (Ins) in the cerebellar hemisphere (51%) and pons (46%). No changes of Asp and Ins were detected in SCA14. Beyond, glucose (Glc) was increased in the vermis of both SCA14 (155%) and SCA1 (247%). 1H magnetic resonance spectroscopy revealed differing neurochemical profiles in SCA1 and SCA14 and confirmed metabolic changes that may be indicative for neuronal loss and dysfunctional energy metabolism. Therefore, 1H magnetic resonance spectroscopy represents a helpful tool for in-vivo tracking of disease-specific pathophysiology