Proton Magnetic Resonance Spectroscopy and Illness Stage in Schizophrenia-A Systematic Review and Meta-Analysis

Background It is not known whether regional brain N-acetyl aspartate (NAA) changes in the progression from prodrome to chronic schizophrenia. We used effect size meta-analysis to determine which brain regions show the most robust reductions in NAA first episode and chronic schizophrenia as measured by proton magnetic resonance spectroscopy and to determine whether these changes are present in individuals at high risk of developing schizophrenia. Methods We identified 131 articles, of which 97 met inclusion criteria. Data were separated by stage of illness (at risk, first episode schizophrenia, chronic schizophrenia) and by brain region. For each region, mean and SD of the NAA measure was extracted. Results Significant reductions in NAA levels were found in frontal lobe, temporal lobe, and thalamus in both patient groups (effect size > .3; p < .01). In individuals at high risk of schizophrenia (of whom approximately 20% would be expected to undergo transition to psychosis), significant NAA reductions were present in thalamus (effect size = .78; p < .05), with reductions at trend level only in temporal lobe (effect size = .32; p < .1), and no reductions in frontal lobe (effect size = .05; p = .5). Conclusions These data suggest that schizophrenia is associated with loss of neuronal integrity in frontal and temporal cortices and in the thalamus and suggest that these changes in the frontal and temporal lobe might occur in the transition between the at-risk phase and the first episode

Synthesis and Characterization of Novel Stationary Phases for Model and Catalytic Reactions in Interphases and New Polysiloxane Matrices

Im ersten Teil der Arbeit wurde das T-funktionalisierte 1,3–bis(diphenylphosphinyl)– propane [(MeO)3Si(CH2)6CH(CH2PPh2)2; PP(T0)] mit den D-bifunktionalisierten Cokondensaten MeSi(OMe)2(CH2)6(MeO)2SiMe (D0–C6–D0) und MeSi(OMe)2(CH)3(C6H4)(CH2)3(MeO)2SiMe [Ph(1,4–C3D0)2] in zwei unterschiedlichen Stöchiometrien sol-gel prozessiert. Um die dynamischen Eigenschaften von diesen polysiloxan-gebundenen Diphosliganden zu untersuchen, wurden detaillierte 29Si and 31P CP/MAS NMR Messungen durchgeführt. Die Zugänglichkeit der P-Zentren in den Xerogelen [PP(Tn)](Di–C6–Di)5 und [PP(Tn)][Ph(1,4–C3Di)2]5 wurden mittels klassischen Phosphanreaktionen untersucht. Im zweiten Teil dieser Arbeit wurde der T-funktionalisierte (COD)Rh(dppp)-Komplex {(C8H12)Rh[(Ph2PCH2)2CH(CH2)6Si(OMe)3]}[SbF6] {(COD)Rh[PP(T0)]} in einer Eintopfreaktion synthetisiert und mit unterschiedlichen Mengen der Cokondensate D0–C6–D0 und Ph(1,4–C3D0)2 sol-gel prozessiert. Die Zugänglichkeit der katalytisch aktiven Zentren wurde mittels Hydierung von 1-Hexen untersucht. Alle Komplexe zeigten dabei gute Aktivitäten, wobei eine Steigerung des Umsatzes durch Verwendung polarer Solventien erzielt werden konnte. Alle Komplexe zeigten eine hohe Standfestigkeit und keinerlei Leaching. Der dritte Teil dieser Dissertation beschäftigt sich mit der Synthese von neuartigen Cokondensaten R2Si(C3D0)2 [MeSi(OMe)2(CH2)3SiR2(CH2)3(OMe)2SiMe; R = Me, Et] und R2Si(C3T0)2 [(MeO)3Si(CH2)3SiR2(CH2)3Si(OMe)3; R = Me, Et]. Nach der Sol-gel-Prozessierung mit und ohne Phenyltrimethoxysilan wurden die erhaltenen Xerogele mittels Festkörper-NMR und Suspensions-NMR Spektroskopie untersucht.In the first chapter of this thesis the T–functionalized 1,3–bis(diphenylphosphinyl)– propane [(MeO)3Si(CH2)6CH(CH2PPh2)2; PP(T0)] was sol–gel processed with the D–bifunctionalized co–condensing agents MeSi(OMe)2(CH2)6(MeO)2SiMe (D0–C6–D0) and MeSi(OMe)2(CH)3(C6H4)(CH2)3(MeO)2SiMe [Ph(1,4–C3D0)2] in two different ratios to yield the polysiloxane–bound diphos ligands [PP(Tn)](Di–C6–Di)y (y = 2.5, 5) and [PP(Tn)][Ph(1,4–C3Di)2]y (y = 2.5, 5). For the investigation of the dynamic properties of the polysiloxane–bound ligands detailed 29Si and 31P CP/MAS NMR relaxation time studies were carried out. To scrutinize the accessibility of the phosphorus centers in these different kinds of stationary phases both polysiloxane–bound diphos ligands [PP(Tn)](Di–C6–Di)5 and [PP(Tn)][Ph(1,4–C3Di)2]5 were subjected to various classical phosphine reactions. The second part of the work features the synthesis and characterization of a (COD)diphosphinerhodium(I) complex bound to a polysiloxane network and accessibility studies by the catalytic hydrogenation of 1–hexene. The monomeric precursor complex {(C8H12)Rh[(Ph2PCH2)2CH(CH2)6Si(OMe)3]}[SbF6] {(COD)Rh[PP(T0)]} was synthesized in a one–pot reaction starting from [µ–ClRh(COD)]2 by consecutive chloride abstraction with AgSbF6 and addition of the T–functionalized diphos ligand (MeO)3Si(CH2)6CH(CH2PPh2)2 [PP(T0)]. This complex was sol–gel processed with various amounts of the co–condensing agents D0–C6–D0 and Ph(1,4–C3D0)2 to give the novel stationary phases {(COD)Rh[PP(Tn)]}(Di–C6–Di)y (y = 0, 2.5, 5, 10, 20) and {(COD)Rh[PP(Tn)]}[Ph(1,4–C3Di)2]y (y = 0, 2.5, 5, 10, 20). The accessibility of the polysiloxane–bound diphosphinerhodium(I) complexes was investigated by the catalytic hydrogenation of 1–hexene. All applied complexes show rather good turnover frequencies and are therefore readily accessible for substrates. An enhancement of the conversion rate was achieved by the use of polar solvents (1,4–dioxane, methanol). If the ca

Applying the energy efficiency first principle based on a decision-tree framework

Energy Efficiency First (EEF) is an established principle for European Union (EU) energy policy design. It highlights the exploitation of demand-side resources and prioritizes cost-effective options from the demand-side over other options from a societal cost-benefit perspective. However, the involvement of multiple decision-makers makes it difficult to implement. Therefore, we propose a flexible decision-tree framework for applying the EEF principle based on a review of relevant areas and examples. In summary, this paper contributes to applying the EEF principle by defining and distinguishing different types of cases - (1) policy-making, and (2) system planning and investment - identifying the most common elements, and proposing a decision-tree framework that can be flexibly constructed based on the elements for different cases. Finally, we exemplify the application of this framework with two example cases: (1) planning for demand-response in the power sector, and (2) planning for a district heating system

A Pronounced Spike in Ocean Productivity Triggered by the Chicxulub Impact

There is increasing evidence linking the mass-extinction event at the Cretaceous-Paleogene boundary to an asteroid impact near Chicxulub, Mexico. Here we use model simulations to explore the combined effect of sulfate aerosols, carbon dioxide and dust from the impact on the oceans and the marine biosphere in the immediate aftermath of the impact. We find a strong temperature decrease, a brief algal bloom caused by nutrients from both the deep ocean and the projectile, and moderate surface ocean acidification. Comparing the modeled longer-term post-impact warming and changes in carbon isotopes with empirical evidence points to a substantial release of carbon from the terrestrial biosphere. Overall, our results shed light on the decades to centuries after the Chicxulub impact which are difficult to resolve with proxy data

Conditional gene deletion reveals functional redundancy of GABAB receptors in peripheral nociceptors in vivo

Background Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter which mainly mediates its effects on neurons via ionotropic (GABAA) and metabotropic (GABAB) receptors. GABAB receptors are widely expressed in the central and the peripheral nervous system. Although there is evidence for a key function of GABAB receptors in the modulation of pain, the relative contribution of peripherally- versus centrally-expressed GABAB receptors is unclear. Results In order to elucidate the functional relevance of GABAB receptors expressed in peripheral nociceptive neurons in pain modulation we generated and analyzed conditional mouse mutants lacking functional GABAB(1) subunit specifically in nociceptors, preserving expression in the spinal cord and brain (SNS-GABAB(1)-/- mice). Lack of the GABAB(1) subunit precludes the assembly of functional GABAB receptor. We analyzed SNS-GABAB(1)-/- mice and their control littermates in several models of acute and neuropathic pain. Electrophysiological studies on peripheral afferents revealed higher firing frequencies in SNS-GABAB(1)-/- mice compared to corresponding control littermates. However no differences were seen in basal nociceptive sensitivity between these groups. The development of neuropathic and chronic inflammatory pain was similar across the two genotypes. The duration of nocifensive responses evoked by intraplantar formalin injection was prolonged in the SNS-GABAB(1)-/- animals as compared to their control littermates. Pharmacological experiments revealed that systemic baclofen-induced inhibition of formalin-induced nociceptive behaviors was not dependent upon GABAB(1) expression in nociceptors. Conclusion This study addressed contribution of GABAB receptors expressed on primary afferent nociceptive fibers to the modulation of pain. We observed that neither the development of acute and chronic pain nor the analgesic effects of a systematically-delivered GABAB agonist was significantly changed upon a specific deletion of GABAB receptors from peripheral nociceptive neurons in vivo. This lets us conclude that GABAB receptors in the peripheral nervous system play a less important role than those in the central nervous system in the regulation of pain

Altered activation and connectivity of the supplementary motor cortex at motor initiation in Parkinson's disease patients with freezing

OBJECTIVE Motor initiation failure is a key feature of freezing of gait (FOG) due to Parkinson's disease (PD). The supplementary motor cortex (SMC) plays a central role in its pathophysiology. We aimed at investigating SMC activation, connectivity and plasticity with regard to motor initiation in FOG. METHODS Twelve patients with FOG and eleven without FOG underwent a multimodal electrophysiological evaluation of SMC functioning including the Bereitschaftspotential and movement-related desynchronisation of cortical beta oscillations. SMC plasticity was modulated by intermittent theta burst stimulation (iTBS) and its impact on gait initiation was assessed by a three-dimensional gait analysis. RESULTS Prior to volitional movements the Bereitschaftspotential was smaller and beta power was less strongly attenuated over the SMC in patients with FOG compared to those without. Pre-motor coherence between the SMC and the primary motor cortex in the beta frequency range was also stronger in patients with FOG. iTBS resulted in a relative deterioration of gait initiation. CONCLUSIONS Reduced activation of the SMC along with increased SMC connectivity in the beta frequency range hinder a flexible shift of the motor set as it is required for gait initiation. SIGNIFICANCE Altered SMC functioning plays an important role for motor initiation failure in PD-related FOG

Interventional treatment of mitral valve regurgitation: an alternative to surgery?

Mitral regurgitation is a highly prevalent condition among elderly patients, affecting almost 10% of the general population aged 75 and older. Left untreated, severe mitral regurgitation results in high mortality and frequent hospitalisation for treatment of heart failure. Surgical treatment remains the first-line therapy for symptomatic, severe mitral regurgitation , especially for patients presenting with a primary aetiology. However, a high proportion of patients with mitral regurgitation are turned down for open-heart surgery, mainly due to advanced age, diminished left ventricular function and comorbidities. Thus, percutaneous treatment options have been recently developed as an alternative. In this article, we will review transcatheter interventional techniques at the level of the mitral valve, including implantation technique, indications and clinical results

A cross-sectional MR study of body fat volumes and distribution in chronic schizophrenia

Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265AbstractPeople with schizophrenia show higher risk for abdominal obesity than the general population, which could contribute to excess mortality. However, it is unclear whether this is driven by alterations in abdominal fat partitioning. Here, we test the hypothesis that individuals with schizophrenia show a higher proportion of visceral to total body fat measured using magnetic resonance imaging (MRI). We recruited 38 participants with schizophrenia and 38 healthy controls matched on age, sex, ethnicity, and body mass index. We found no significant differences in body fat distribution between groups, suggesting that increased abdominal obesity in schizophrenia is not associated with altered fat distribution.</jats:p

Rule Extraction From Binary Neural Networks With Convolutional Rules for Model Validation

Classification approaches that allow to extract logical rules such as decision trees are often considered to be more interpretable than neural networks. Also, logical rules are comparatively easy to verify with any possible input. This is an important part in systems that aim to ensure correct operation of a given model. However, for high-dimensional input data such as images, the individual symbols, i.e. pixels, are not easily interpretable. Therefore, rule-based approaches are not typically used for this kind of high-dimensional data. We introduce the concept of first-order convolutional rules, which are logical rules that can be extracted using a convolutional neural network (CNN), and whose complexity depends on the size of the convolutional filter and not on the dimensionality of the input. Our approach is based on rule extraction from binary neural networks with stochastic local search. We show how to extract rules that are not necessarily short, but characteristic of the input, and easy to visualize. Our experiments show that the proposed approach is able to model the functionality of the neural network while at the same time producing interpretable logical rules. Thus, we demonstrate the potential of rule-based approaches for images which allows to combine advantages of neural networks and rule learning