Assessment of successful incorporation of cages after cervical or lumbar intercorporal fusion with [(18)F]fluoride positron-emission tomography/computed tomography

The purpose of this study is to assess the successful incorporation of cages in patients after cervical or lumbar intercorporal fusion with positron-emission tomography/computed tomography (PET/CT). Twenty patients (14 female and 6 male; mean age 58years, age range 38-73years) with 30 cervical (n=13) or lumbar (n=17) intercorporal fusions were prospectively enrolled in this study. Time interval between last intercorporal intervention and PET/CT ranged from 2 to 116months (mean 63; median 77months). IRB approval was obtained for all patients, and written informed consent was obtained from all patients. About 30min prior to PET/CT scanning, 97-217MBq (mean 161MBq) 18F-fluoride were administered intravenously. Patients were imaged in supine position on a combined PET/CT system (Discovery RX/STE, 16/64 slice CT, GE Healthcare). 3D-PET emission data were acquired for 1.5 and 2min/bed position, respectively, and reconstructed by a fully 3D iterative algorithm (VUE Point HD) using low-dose CT data for attenuation correction. A dedicated diagnostic thin-slice CT was optionally acquired covering the fused region. Areas of increased 18F-fluoride uptake around cages were determined by one double-board certified radiologist/nuclear physician and one board certified radiologist in consensus. In 12/20 (60%) patients, increased 18F-fluoride uptake around cages was observed. Of the 30 intercorporal fusions, 15 (50%) showed increased 18F-fluoride uptake. Median time between intervention and PET/CT examination in cages with increased uptake was 37months (2-116months), median time between intervention and PET/CT examination in those cages without increased uptake was 91months (19-112months), p (Wilcoxon)=0.01 (one-sided). 14/29 (48%) cages with a time interval>1year between intervention and PET/CT scan showed an increased uptake. In conclusion, PET/CT frequently shows increased 18F-fluoride uptake in cervical and lumbar cages older than 1year (up to almost 8years in cervical cages and 10years in lumbar cages) possibly indicating unsuccessful fusion due to increased stress/microinstabilit

S66: A Well-balanced Database of Benchmark Interaction Energies Relevant to Biomolecular Structures

With numerous new quantum chemistry methods being developed in recent years and the promise of even more new methods to be developed in the near future, it is clearly critical that highly accurate, well-balanced, reference data for many different atomic and molecular properties be available for the parametrization and validation of these methods. One area of research that is of particular importance in many areas of chemistry, biology, and material science is the study of noncovalent interactions. Because these interactions are often strongly influenced by correlation effects, it is necessary to use computationally expensive high-order wave function methods to describe them accurately. Here, we present a large new database of interaction energies calculated using an accurate CCSD(T)/CBS scheme. Data are presented for 66 molecular complexes, at their reference equilibrium geometries and at 8 points systematically exploring their dissociation curves; in total, the database contains 594 points: 66 at equilibrium geometries, and 528 in dissociation curves. The data set is designed to cover the most common types of noncovalent interactions in biomolecules, while keeping a balanced representation of dispersion and electrostatic contributions. The data set is therefore well suited for testing and development of methods applicable to bioorganic systems. In addition to the benchmark CCSD(T) results, we also provide decompositions of the interaction energies by means of DFT-SAPT calculations. The data set was used to test several correlated QM methods, including those parametrized specifically for noncovalent interactions. Among these, the SCS-MI-CCSD method outperforms all other tested methods, with a root-mean-square error of 0.08 kcal/mol for the S66 data set

Charge Transfer from Regularized Symmetry-Adapted Perturbation Theory

16 pages, 16 figure

Voltooid leven: Over hulp bij zelfdoding aan mensen die hun leven voltooid achten

Criminal Justice: Legitimacy, accountability, and effectivit

Reduction in Inter-Hemispheric Connectivity in Disorders of Consciousness

Clinical diagnosis of disorders of consciousness (DOC) caused by brain injury poses great challenges since patients are often behaviorally unresponsive. A promising new approach towards objective DOC diagnosis may be offered by the analysis of ultra-slow (<0.1 Hz) spontaneous brain activity fluctuations measured with functional magnetic resonance imaging (fMRI) during the resting-state. Previous work has shown reduced functional connectivity within the “default network”, a subset of regions known to be deactivated during engaging tasks, which correlated with the degree of consciousness impairment. However, it remains unclear whether the breakdown of connectivity is restricted to the “default network”, and to what degree changes in functional connectivity can be observed at the single subject level. Here, we analyzed resting-state inter-hemispheric connectivity in three homotopic regions of interest, which could reliably be identified based on distinct anatomical landmarks, and were part of the “Extrinsic” (externally oriented, task positive) network (pre- and postcentral gyrus, and intraparietal sulcus). Resting-state fMRI data were acquired for a group of 11 healthy subjects and 8 DOC patients. At the group level, our results indicate decreased inter-hemispheric functional connectivity in subjects with impaired awareness as compared to subjects with intact awareness. Individual connectivity scores significantly correlated with the degree of consciousness. Furthermore, a single-case statistic indicated a significant deviation from the healthy sample in 5/8 patients. Importantly, of the three patients whose connectivity indices were comparable to the healthy sample, one was diagnosed as locked-in. Taken together, our results further highlight the clinical potential of resting-state connectivity analysis and might guide the way towards a connectivity measure complementing existing DOC diagnosis

Dynamic Changes in Brain Functional Connectivity during Concurrent Dual-Task Performance

This study investigated the spatial, spectral, temporal and functional proprieties of functional brain connections involved in the concurrent execution of unrelated visual perception and working memory tasks. Electroencephalography data was analysed using a novel data-driven approach assessing source coherence at the whole-brain level. Three connections in the beta-band (18–24 Hz) and one in the gamma-band (30–40 Hz) were modulated by dual-task performance. Beta-coherence increased within two dorsofrontal-occipital connections in dual-task conditions compared to the single-task condition, with the highest coherence seen during low working memory load trials. In contrast, beta-coherence in a prefrontal-occipital functional connection and gamma-coherence in an inferior frontal-occipitoparietal connection was not affected by the addition of the second task and only showed elevated coherence under high working memory load. Analysis of coherence as a function of time suggested that the dorsofrontal-occipital beta-connections were relevant to working memory maintenance, while the prefrontal-occipital beta-connection and the inferior frontal-occipitoparietal gamma-connection were involved in top-down control of concurrent visual processing. The fact that increased coherence in the gamma-connection, from low to high working memory load, was negatively correlated with faster reaction time on the perception task supports this interpretation. Together, these results demonstrate that dual-task demands trigger non-linear changes in functional interactions between frontal-executive and occipitoparietal-perceptual cortices

π-π stacking tackled with density functional theory

Through comparison with ab initio reference data, we have evaluated the performance of various density functionals for describing π-π interactions as a function of the geometry between two stacked benzenes or benzene analogs, between two stacked DNA bases, and between two stacked Watson–Crick pairs. Our main purpose is to find a robust and computationally efficient density functional to be used specifically and only for describing π-π stacking interactions in DNA and other biological molecules in the framework of our recently developed QM/QM approach "QUILD". In line with previous studies, most standard density functionals recover, at best, only part of the favorable stacking interactions. An exception is the new KT1 functional, which correctly yields bound π-stacked structures. Surprisingly, a similarly good performance is achieved with the computationally very robust and efficient local density approximation (LDA). Furthermore, we show that classical electrostatic interactions determine the shape and depth of the π-π stacking potential energy surface