Influence of respiration-induced B0 variations in real-time phase-contrast echo planar imaging of the cervical cerebrospinal fluid.

PURPOSE: Respiration induces temporal variations of the main magnetic field B0 along the spinal cord. These variations are typically not compensated for in velocity quantifications using phase-contrast MRI. The goal of this study was to analyze errors caused by respiration-induced B0 variations in real-time phase-contrast echo planar imaging (PCEPI) of cervical cerebrospinal fluid (CSF) velocity measurements and to evaluate this effect for various sequence parameters using numerical simulations. METHODS: Real-time B0 measurements with double gradient echo sequence and PCEPI measurements were acquired in the cervical CSF of 10 healthy subjects. Dynamic phase offsets attributed to respiration-induced B0 variations were analyzed by quantifying amplitudes and comparing the temporal behavior with respiratory signals. In experiments and simulations, the influence of the echo time (TE) and the delay between PCEPI images (Δt) with respect to respiration on the dynamic phase offsets were investigated. RESULTS: A good agreement was found between phase offsets extracted from both acquisition types. Furthermore, respiratory signals qualitatively matched the temporal behavior of the measured phase offsets showing a dependency on subject-dependent local B0 distribution and respiration physiology. Simulations revealed residual background phases in PCEPI velocity quantification varying with TE and Δt. CONCLUSION: Respiration-induced B0 variations result in dynamic background phases in real-time PCEPI velocity quantifications of the CSF in the cervical spine. The current work underlines that these background phases need to be corrected to avoid confounding effects.

Oriented Films of Conjugated 2D Covalent Organic Frameworks as Photocathodes for Water Splitting.

Light-driven water electrolysis at a semiconductor surface is a promising way to generate hydrogen from sustainable energy sources, but its efficiency is limited by the performance of available photoabsorbers. Here we report the first time investigation of covalent organic frameworks (COFs) as a new class of photoelectrodes. The presented 2D-COF structure is assembled from aromatic amine-functionalized tetraphenylethylene and thiophene-based dialdehyde building blocks to form conjugated polyimine sheets, which π-stack in the third dimension to create photoactive porous frameworks. Highly oriented COF films absorb light in the visible range to generate photoexcited electrons that diffuse to the surface and are transferred to the electrolyte, resulting in proton reduction and hydrogen evolution. The observed photoelectrochemical activity of the 2D-COF films and their photocorrosion stability in water pave the way for a novel class of photoabsorber materials with versatile optical and electronic properties that are tunable through the selection of appropriate building blocks and their three-dimensional stacking.

Esomeprazole FDA Approval in Children With GERD: Exposure-Matching and Exposure-Response.

OBJECTIVES: Food and Drug Administration approval of proton-pump inhibitors for infantile gastroesophageal reflux disease has been limited by intrapatient variability in the clinical assessment of gastroesophageal reflux disease. For children 1 to 17 years old, extrapolating efficacy from adults for IV esomeprazole was accepted. The oral formulation was previously approved in children. Exposure-response and exposure matching analyses were sought to identify approvable pediatric doses. METHODS: Intragastric pH biomarker comparisons between children and adults were conducted. Pediatric doses were selected to match exposures in adults and were based on population pharmacokinetic (PK) modeling and simulations with pediatric esomeprazole data. Observed IV or oral esomeprazole PK data were available from 50 and 117 children, between birth and 17 years, respectively, and from 65 adults, between 20 and 48 years. A population PK model developed using these data was used to simulate steady-state esomeprazole exposures for children at different doses to match the observed exposures in adults. RESULTS: Exposure-response relationships of intragastric pH measures were similar between children and adults. The PK simulations identified a dosing regimen for children that results in comparable steady-state area under the curve to that observed after 20 mg in adults. For IV esomeprazole, increasing the infusion duration to 10 to 30 minutes in children achieves matching Cmax values with adults. CONCLUSIONS: The exposure-matching analysis permitted approval of an esomeprazole regimen not studied directly in clinical trials. Exposure-response for intragastric pH-permitted approval for the treatment of gastroesophageal reflux disease in children in whom it was not possible to evaluate the adult primary endpoint, mucosal healing assessed by endoscopy.

Black Magic in Gray Titania: Noble-Metal-Free Photocatalytic H2 Evolution from Hydrogenated Anatase.

'Black' TiO2 -in the widest sense, TiO2 reduced by various treatments-has attracted tremendous scientific interest in recent years because of some outstanding properties; most remarkably in photocatalysis. While the material effects visible light absorption (the blacker, the better), black titania produced by high pressure hydrogenation was recently reported to show another highly interesting feature; noble-metal-free photocatalytic H2 generation. In a systematic investigation of high-temperature hydrogen treatments of anatase nanoparticles, TEM, XRD, EPR, XPS, and photoelectrochemistry are used to characterize different degrees of surface hydrogenation, surface termination, electrical conductivity, and structural defects in the differently treated materials. The materials' intrinsic activity for photocatalytic hydrogen evolution is coupled neither with their visible light absorption behavior nor the formation of amorphous material, but rather must be ascribed to optimized and specific defect formation (gray is better than black). This finding is further confirmed by using a mesoporous anatase matrix as a hydrogenation precursor, which, after conversion to the gray state, even further enhances the overall photocatalytic hydrogen evolution activity.

Ablation of clinically relevant kidney tissue volumes by high-intensity focused ultrasound: Preliminary results of standardized ex-vivo investigations.

PURPOSE: To investigate strategies to achieve confluent kidney-tissue ablation by high-intensity focused ultrasound (HIFU). MATERIALS AND METHODS: Our model of the perfused ex-vivo porcine kidney was used. Tissue ablation was performed with an experimental HIFU device (Storz Medical, Kreuzlingen, Switzerland). Lesion-to-lesion interaction was investigated by varying the lesion distance (5 to 2.5 mm), generator power (300, 280, and 260 W), cooling time (10, 20, and 30 seconds), and exposure time (4, 3, and 2 seconds). The lesion rows were analyzed grossly and by histologic examination (hematoxylin-eosin and nicotinamide adenine dinucleotide staining). RESULTS: It was possible to achieve complete homogeneous ablation of a clinically relevant tissue volume but only by meticulous adjustment of the exposure parameters. Minimal changes in these parameters caused changes in lesion formation with holes within the lesions and lesion-to-lesion interaction. CONCLUSIONS: Our preliminary results show that when using this new device, HIFU can ablate a large tissue volume homogeneously in perfused ex-vivo porcine tissue under standardized conditions with meticulous adjustment of exposure parameters. Further investigations in vivo are necessary to test whether large tissue volumes can be ablated completely and reliably despite the influence of physiologic tissue and organ movement.

Magnetic resonance imaging for assessment of radiofrequency lesions in kidney tissue immediately after ablation: an experimental study.

BACKGROUND AND PURPOSE: Radiofrequency ablation (RFA) is an attractive minimally invasive treatment option for small renal masses. The purpose of this study was to investigate the morphologic imaging appearance of RF lesions immediately after the ablation of kidney tissue using standard clinical MR sequences, as well as to investigate the correlation between MR and gross lesion size. MATERIALS AND METHODS: Ablations were performed 17 times in a standardized model of ex-vivo perfused porcine kidneys using a resistance-controlled RF device (250 W, 470 kHz) and a nonexpandable bipolar applicator inserted into the center of healthy renal parenchyma. The RF current was applied for 9 minutes at 20 W. Imaging was performed after ablation using standard clinical MR sequences: morphologic T(1)/T(2)- weighted images and an isotropic post-contrast T(1) high-resolution measurement (VIBE). Maximum lesion diameters were measured in three directions and were compared with the measurements of the gross lesions. Histologic (hematoxylin + eosin and nicotinamide adenine dinucleotide staining) and statistical analyses were performed. RESULTS: The gross pathologic examination showed a firm, white-yellow ablation zone sharply demarcated from the untreated tissue. The histologic examination confirmed cellular viability outside but not in the treatment zone. The RF lesions were hyperintense on T(1)-weighted images and hypointense on T(2)-weighted images. The lesion size measured in the VIBE images correlated best with the macroscopic lesion size (N = 16). CONCLUSIONS: Morphologic MR T(1) and T(2) sequences of RF lesions immediately after ablation produce reliable and consistent imaging characteristics. The post-contrast, high-resolution sequence (VIBE) enables the extent of the lesion to be determined accurately. The potential uses of this imaging strategy in clinical practise warrant further investigation on human renal-cell carcinoma.

Control of Perovskite Crystal Growth by Methylammonium Lead Chloride Templating.

State-of-the-art solar cells based on methylammonium lead iodide (MAPbI3 ) now reach efficiencies over 20 %. This fast improvement was possible with intensive research in perovskite processing. In particular, chloride-based precursors are known to have a positive influence on the crystallization of the perovskite. Here, we used a combination of in-situ X-ray diffraction and charge-transport measurements to understand the influence of chloride during perovskite crystallization in planar heterojunction solar cells. We show that MAPbCl3 crystallizes directly after the deposition of the starting solution and acts as a template for the formation of MAPbI3 . Additionally, we show that the charge-carrier mobility doubles by extending the time for the template formation. Our results give a deeper understanding of the influence of chloride in the synthesis of MAPbI3 and illustrate the importance of carefully controlling crystallization for reproducible, high-efficiency solar cells.

The influence of the dopaminergic system on cognitive functioning: A molecular genetic approach.

Many pharmacological and clinical studies have demonstrated the importance of the dopaminergic (DA) system for cognitive functioning but little is known about the genetic basis of general cognitive ability that has been demonstrated to be highly heritable. Attempts to detect associations between certain gene loci and endophenotypes of general cognitive ability have turned out to be more promising. Therefore, the aim of the present study was to investigate two dopaminergic candidate genes (COMT VAL158MET and DRD2 TAQ IA) for endophenotypes of cognitive functioning i.e. attention, vigilance, interference, time estimation and sensoric and motoric reaction times. Out of a gene data bank of more than 600 healthy Caucasian participants, 96 subjects (n = 48 males and n = 48 females) were recruited according to their genotype/allele pattern, resulting in six independent groups (COMT: VAL/VAL, VAL/MET, MET/MET)x(DRD2: A1-, A1+) of n = 16 subjects each. Results showed associations of the COMT gene with attention and with time estimation but most noteworthy was an interaction effect DRD2xVAL on interference performance as measured by the STROOP-test explaining 13% of the variance. Findings suggest that a balance between DA related catabolic enzyme activity and receptor density are good predictors for the endophenotype of cognitive interference and that the COMT gene is in accordance with previous studies related to cognitive functioning.

Multiple high-intensity focused ultrasound probes for kidney-tissue ablation.

BACKGROUND AND PURPOSE: To investigate kidney-tissue ablation by high-intensity focused ultrasound (HIFU) using multiple and single probes. MATERIALS AND METHODS: Ultrasound beams (1.75 MHz) produced by a piezoceramic element (focal distance 80 mm) were focused at the center of renal parenchyma. One of the three probes (mounted on a jig) could also be used for comparison with a single probe at comparable power ratings. Lesion dimensions were examined in perfused and unperfused ex vivo porcine kidneys at different power levels (40, 60, and 80 W) and treatment times (4, 6, and 8 seconds). RESULTS: At identical power levels, the lesions induced by multiple probes were larger than those induced by a single probe. Lesion size increased with increasing pulse duration and generator power. The sizes and shapes of the lesions were predictably repeatable in all samples. Lesions in perfused kidneys were smaller than those in unperfused kidneys. CONCLUSIONS: Ex vivo, kidney-tissue ablation by means of multiple HIFU probes offers significant advantages over single HIFU probes in respect of lesion size and formation. These advantages need to be confirmed by tests in vivo at higher energy levels.

3D-electrode architectures for enhanced direct bioelectrocatalysis of pyrroloquinoline quinone-dependent glucose dehydrogenase.

We report on the fabrication of a complex electrode architecture for efficient direct bioelectrocatalysis. In the developed procedure, the redox enzyme pyrroloquinoline quinone-dependent glucose dehydrogenase entrapped in a sulfonated polyaniline [poly(2-methoxyaniline-5-sulfonic acid)-co-aniline] was immobilized on macroporous indium tin oxide (macroITO) electrodes. The use of the 3D-conducting scaffold with a large surface area in combination with the conductive polymer enables immobilization of large amounts of enzyme and its efficient communication with the electrode, leading to enhanced direct bioelectrocatalysis. In the presence of glucose, the fabricated bioelectrodes show an exceptionally high direct bioelectrocatalytical response without any additional mediator. The catalytic current is increased more than 200-fold compared to planar ITO electrodes. Together with a high long-term stability (the current response is maintained for >90% of the initial value even after 2 weeks of storage), the transparent 3D macroITO structure with a conductive polymer represents a valuable basis for the construction of highly efficient bioelectronic units, which are useful as indicators for processes liberating glucose and allowing optical and electrochemical transduction.

The modulatory influence of the functional COMT Val158Met polymorphism on lexical decisions and semantic priming.

The role of the prefrontal Cortex (PFC) in higher cognitive functions - including working memory, conflict resolution, set shifting and semantic processing - has been demonstrated unequivocally. Despite the great heterogeneity among tasks measuring these phenotypes, due in part to the different cognitive sub-processes implied and the specificity of the stimulus material used, there is agreement that all of these tasks recruit an executive control system located in the PFC. On a biochemical level it is known that the dopaminergic system plays an important role in executive control functions. Evidence comes from molecular genetics relating the functional COMT Val158Met polymorphism to working memory and set shifting. In order determine whether this pattern of findings generalises to linguistic and semantic processing, we investigated the effects of the COMT Val158Met polymorphism in lexical decision making using masked and unmasked versions of the semantic priming paradigm on N = 104 healthy subjects. Although we observed strong priming effects in all conditions (masked priming, unmasked priming with short/long stimulus asynchronies (SOAs), direct and indirect priming), COMT was not significantly related to priming, suggesting no reliable influence on semantic processing. However, COMT Val158Met was strongly associated with lexical decision latencies in all priming conditions if considered separately, explaining between 9 and 14.5% of the variance. Therefore, the findings indicate that COMT mainly influences more general executive control functions in the PFC supporting the speed of lexical decisions.

Magnetic resonance imaging as a technique for assessing noninvasive tissue ablation using high-intensity ultrasound: an experimental study.

BACKGROUND AND PURPOSE: As a form of noninvasive extracorporeal application, acoustic energy offers an alternative to nephron-sparing surgery for renal masses smaller than 4 cm. The availability of a reliable tool for monitoring the therapy is a prerequisite for safe and successful high-intensity focused ultrasound (HIFU) application. The aim of this study was to evaluate the morphologic visualization of HIFU lesions using MRI. MATERIALS AND METHODS: We used the ex vivo model of the isolated perfused porcine kidney. Treatment was performed using an experimental HIFU system. Complex lesions were induced in 10 kidneys. MRI was performed under constant perfusion of the kidneys. To determine the exact lesion size, we performed a fat-saturated, T1-weighted, volumetric interpolated breath-hold MRI sequence. For perfusion imaging, we used a three-dimensional fast low-angle shot sequence. Subsequently, the lesions were evaluated macroscopically. The width of the complex lesions was defined as x, the length as y, and the depth as z. RESULTS: The MRI scans showed good soft tissue contrast in all sequences. The mean difference for the width of the lesions was 0.2 +/- 1.1 mm; for lesion length and depth, it was 1.7 +/- 1.8 mm and 1.1 +/- 1.3 mm for lesion width, respectively. Statistical evaluation of the x values showed no significant difference between the macroscopic and the MRI data (P = 0.85). The y and z values, however, showed a statistically significant difference (P = 0.071). CONCLUSION: MRI could be a diagnostic tool for monitoring HIFU. Before this modality can be used under clinical conditions, further technical development is indispensable, especially with respect to reducing the measuring times.

[The isolated perfused porcine kidney model for investigations concerning surgical therapy procedures]. / Das Modell der isolierten perfundierten Schweineniere zur Erforschung chirurgischer Therapieverfahren.

Experiments to develop innovative surgical therapy procedures are conventionally conducted on animals, as crucial aspects like tissue removal and bleeding disposition cannot be investigated in vitro. Extracorporeal organ models however reflect these aspects and could thus reduce the use of animals for this purpose fundamentally in the future. The aim of this work was to validate the isolated perfused porcine kidney model with regard to its use for surgical purposes on the basis of histological and radiological procedures. The results show that neither storage nor artificial perfusion led to any structural or functional damage which would affect the quality of the organ. The kidney model is highly suitable for simulating the main aspects of renal physiology and allows a constant calibration of perfusion pressure and tissue temperature. Thus, with only a moderate amount of work involved, the kidney model provides a cheap and readily available alternative to conventional animal experiments; it allows standardised experimental settings and provides valid results.