The introduction of silicon carbide as the semiconductor in gas-sensitive field effect devices has disruptively improved this sensor platform extending the operation temperature to more than 600 °C with an increased number of detectable gases. Here, we review recent progress in research and applications, starting with transducer and detection mechanisms, presenting new material combinations as sensing layers for improved selectivity and detection limits down to subparts per billion. We describe how temperature cycled operation combined with advanced data evaluation enables one sensor to act as a sensor array thereby vastly improving selectivity. Field tests require advanced packaging, which is described, and examples of possible applications like selective detection of ammonia for urea injection control in diesel exhausts and toxic volatile organic compounds for indoor air quality monitoring and control are given.

Patients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as TACE and ablation, to prevent tumor progression and dropout and to improve long-term outcome after transplantation. We wanted to prospectively assess feasibility of systemic antitumor treatment with sorafenib as neoadjuvant treatment for hepatocellular carcinoma while waiting for liver transplantation, evaluating tolerability, toxicity and posttransplant morbidity. We also wanted to evaluate perfusion CT parameters to assess tumor properties and response early after start of sorafenib treatment in patients with early hepatocellular carcinoma. Twelve patients assigned for liver transplantation due to hepatocellular carcinoma, within the UCSF and who fulfilled other criteria, were included January 2012–August 2014. After baseline evaluation, sorafenib treatment was started. Treatment was evaluated by perfusion CT at 1, 4 and 12 weeks and thereafter every 8 weeks. Toxicity and quality of life was assessed at 1 and 4 weeks and every 4 weeks thereafter during treatment. Treatment was stopped when patients were prioritized on the transplantation waiting list or when intolerable side effects or tumor progress warranted other treatments. Posttransplant morbidity after 90 days was registered according to Clavien-Dindo. Baseline perfusion CT parameters in the tumors predicted the outcome according to RECIST/mRECIST at three months, but no change in CTp parameters was detected as a result of sorafenib. Sorafenib as neoadjuvant treatment was associated with intolerability and dose reductions. Therefore the prerequisites for evaluation of the sorafenib effect on both CT parameters and tumor response were impaired. This study failed to show changes in CTp parameters during sorafenib treatment. Despite the curative treatment intention, tolerability of neoadjuvant sorafenib treatment before liver transplantation was inadequate in this study. EudraCT number: 2010–024306-36 (date 2011-04-07).

Several lines of evidence support immunotherapy in hepatocellular carcinoma (HCC). We have shown that intratumoral injections of the immune primer ilixadencel (pro-inflammatory allogeneic dendritic cells) are safe in renal-cell carcinoma. Here, we assessed ilixadencel as a single agent and combined with sorafenib in advanced HCC. Of 17 HCC patients enrolled, 12 patients received ilixadencel at the dose of 10 × 106 cells (six as monotherapy and six in combination with sorafenib), and five received ilixadencel at the dose of 20 × 106 cells as monotherapy. The primary objective was to evaluate tolerability. All patients had at least one adverse event, with 30% of such events considered as treatment-related, with one single treatment-related grade three event. The most common toxicity was grade 1 and 2 fever and chills. Eleven of 15 evaluable patients (73%) showed increased frequency of tumor-specific CD8+ T cells in peripheral blood. Overall one patient had a partial response (with ilixadencel as monotherapy), and five had stable disease as overall best response per mRECIST. The median time to progression was 5.5 months, and overall survival ranged from 1.6 to 21.4 months. Our study confirms the safety of ilixadencel as single agent or in combination with sorafenib and indicates tumor-specific immunological responses in advanced HCC. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01974661

Data from a silicon carbide based field-effect transistor were recorded over a period of nine days in a ventilated school room. For enhanced sensitivity and selectivity especially to formaldehyde, porous iridium on pulsed laser deposited tungsten trioxide was used as sensitive layer, in combination with temperature cycled operation and subsequent multivariate data processing techniques. The sensor signal was compared to reference measurements for formaldehyde concentration, CO2 concentration, temperature, and relative humidity. The results show a distinct pattern for the reference formaldehyde concentration, arising from the day/night cycle. Taking this into account, the projections of both principal component analysis and partial least squares regression lead to almost the same result concerning correlation to the reference. The sensor shows cross-sensitivity to an unidentified component of human activity, presumably breath, and, possibly, to other compounds appearing together with formaldehyde in indoor air. Nevertheless, the sensor is able to detect and partially quantify formaldehyde below 40 ppb with a correlation to the reference of 0.48 and negligible interference from ambient temperature or relative humidity.

Incorporation of layers of noble metals in non-van der Waals layered materials may be used to form novel layered compounds. Recently, we demonstrated a high-temperature-induced exchange process of Au with Si in the layered phase Ti3SiC2, resulting in the formation of Ti3AuC2 and Ti3Au2C2. Here, we generalize this technique showing that Au/Ti2AlC and Au/Ti3AlC2 undergo an exchange reaction at 650 °C to form Ti2Au2C and Ti3Au2C2 and determine their structures by electron microscopy, X-ray diffraction, and ab initio calculations. These results imply that noble-metal-containing layered phases should be possible to synthesize in many systems. The metal to be introduced should be inert to the transition-metal carbide layers, and exhibit negative heat of mixing with the initial A element in a liquid phase or two-phase liquid/solid region at the annealing temperature.

In this work, we exposed an MIS capacitor with porous platinum as gate material to different concentrations of CO and NH3. Its capacitance and typical reaction products (water, CO2 and NO) were monitored at high and low oxygen concentration and different gate bias voltages. We found that the gate bias influences the switch-point of the binary CO response usually seen when either changing the temperature at constant gas concentrations or the CO/O2 ratio at constant temperature. For NH3, the sensor response as well as product reaction rates increase with bias voltages up to 6 V. A capacitance overshoot is observed when switching on or off either gas at low gate bias, suggesting increasing oxygen surface coverage with decreasing gate bias.

Temperature cycled operation and multivariate statistics have been used to compare the selectivity of two gate (i.e. sensitive) materials for gas-sensitive, silicon carbide based field effect transistors towards naphthalene and ethanol in different mixtures of the two substances. Both gates have a silicon dioxide (SiO2) insulation layer and a porous iridium (Ir) electrode. One of it has also a dense tungsten trioxide (WO3) interlayer between Ir and SiO2. Both static and transient characteristics play an important role and can contribute to improve the sensitivity and selectivity of the gas sensor.The Ir/SiO2 is strongly influenced by changes in ethanol concentration, and is, thus, able to quantify ethanol in a range between 0 and 5 ppm with a precision of 500 ppb, independently of the naphthalene concentrations applied in this investigation. On the other hand, this sensitivity to ethanol reduces its selectivity towards naphthalene, whereas Ir/WO3/SiO2 shows an almost binary response to ethanol. Hence, the latter has a better selectivity towards naphthalene and can quantify legally relevant concentrations down to 5 ppb with a precision of 2.5 ppb, independently of a changing ethanol background between 0 and 5 ppm. (C) 2016 Elsevier B.V. All rights reserved.

With the increased interest in development of cheap, simple means for indoor air quality monitoring, and specifically in relation to certain well-known pollutant substances with adverse health effects even at very low concentrations, such as different Volatile Organic Compounds (VOCs), this contribution aims at providing an overview of the development status of the silicon carbide field effect transistor (SiC FET) based sensor platform for ppb level detection of VOCs. Optimizing the transducer design, the gas-sensitive material(s) composition, structure and processing, its mode of operation - applying temperature cycled operation in conjunction with multivariate data evaluation - and long-term performance it has been possible to demonstrate promising results regarding the sensor technology's ability to achieve both single-digit ppb sensitivity towards e.g. naphthalene as well as selective detection of individual substances in a mixture of different VOCs.

This study is a short overview on air pollution, its definition, history, and adverse effects on health, environment, and economy, with a particular emphasis on indoor air quality. We demonstrate that gas sensors based on silicon carbide field effect transistor (SiC-FET) technology are suitable for indoor air quality applications due to their high sensitivity, long-term stability, and robustness. Enhancement of selectivity can be reached through the optimization of the sensing layer (gate contact) in combination with smart operation and multivariate statistical methods for data analysis. Formaldehyde, naphthalene, and benzene, belonging to the class of hazardous volatile organic compounds (VOCs), are our target gases at the low parts per billion concentration level.

This contribution treats the latest developments in the understanding of basic principles regarding device design, transduction mechanisms, gas-materials-interactions, and materials processing for the tailored design and fabrication of SiC FET gas sensor devices, mainly intended as products for the automotive sector.

The mastoid air cell system (MACS) with its large complex of interconnected air cells reflects an enhanced surface area (SA) relative to its volume (V), which may indicate that the MACS is adapted to gas exchange and has a potential role in middle ear pressure regulation. These geometric parameters of the MACS have been studied by high resolution clinical CT scanning. However, the resolution of these scans is limited to a voxel size of around 0.6 mm in all dimensions, and so, the geometrical parameters are also limited. Small air cells may appear below the resolution and cannot be detected. Such air cells may contribute to a much higher SA, and thus, also the SA/V ratio. More accurate parameters are important for analysis of the function of the MACS including physiological modeling.Our aim was to determine the SA, V, and SA/V ratio in the MACS in human temporal bones at highest resolution by using micro-CT-scanning. Further, the influence of the resolution on these parameters was investigated by downsampling the data. Eight normally aerated temporal bones were scanned at the highest possible resolution (30-60 mu m). The SA was determined using a triangular mesh fitted onto the segmented MACS. The V was determined by summing all the voxels containing air. Downsampling of the original data was applied four times by a factor of 2.The mean SA was 194 cm(2), the mean V was 9 cm(3), and the mean SA/V amounted to 22 cm(-1) (22 cm(2)/ cm3). Decreasing the resolution resulted in a non-linear decrement of SA and SA/V, whereas V was mainly independent of the resolution.The current study found significantly higher SA and SA/V compared with previous studies using clinical CT scanning at lower resolutions. These findings indicate a role of the MACS different from that of the tympanum, though they are limited to only a smaller sample of temporal bones without knowledge about the disease history of the subjects. The current data on mastoid geometry seems important for a more accurate modeling of the middle ear physiology and future studies may include morphological investigations of the air cells with possible implications for their postnatal development. (C) 2015 Elsevier B.V. All rights reserved.

In image registration it is often necessary to employ regularization in one form or another to be able to find a plausible displacement field.In medical applications, it is useful to define different constraints for different areas of the data.For instance to measure if organs have moved as expected after a finished treatment.One common problem is how to find plausible motion vectors far away from known motion.This paper introduces a new method to build and solve a Global Linear Optimizations (GLO) problem with a novel set of terms which enable specification of border areas to allow a slipping motion.The GLO approach is important especially because it allows simultaneous incorporation of several different constraints using information from medical atlases such as localization and properties of organs.The power and validity of the method is demonstrated using two simple, but relevant 2D test images.Conceptual comparisons with previous methods are also made to highlight the contributions made in this paper.

Recently, numerous micro-channels have been discovered in the human temporal bone by micro-CT-scanning. Preliminary structure of these channels has suggested they contain a new separate blood supply for the mucosa of the mastoid air cells, which may have important functional implications. This paper proposes a structural analysis of the microchannels to corroborate this role. A local structure tensor is first estimated. The eigenvalues obtained from the estimated local structure tensor were then used to build probability maps representing planar, tubular, and isotropic tensor types. Each tensor type was assigned a respective RGB color and the full structure tensor was rendered along with the original data. Such structural analysis provides new and relevant information about the micro-channels but also their connections to mastoid air cells. Before carrying a future statistical analysis, a more accurate representation of the micro-channels in terms of local structure tensor analysis using adaptive filtering is needed.

Radiotherapy planning and attenuation correction of PET images require simulation of radiation transport. The necessary physical properties are typically derived from computed tomography (CT) images, but in some cases, including stereotactic neurosurgery and combined PET/MR imaging, only magnetic resonance (MR) images are available. With these applications in mind, we describe how a realistic, patient-specific, pseudo-CT of the head can be derived from anatomical MR images. We refer to the method as atlas-based regression, because of its similarity to atlas-based segmentation.Given a target MR and an atlas database comprising MR and CT pairs, atlas-based regression works by registering each atlas MR to the target MR, applying the resulting displacement fields to the corresponding atlas CTs and, finally, fusing the deformed atlas CTs into a single pseudo-CT.We use a deformable registration algorithm known as the Morphon and augment it with a certainty mask that allows a tailoring of the influence certain regions are allowed to have on the registration. Moreover, we propose a novel method of fusion, wherein the collection of deformed CTs is iteratively registered to their joint mean and find that the resulting mean CT becomes more similar to the target CT. However, the voxelwise median provided even better results; at least as good as earlier work that required special MR imaging techniques. This makes atlas-based regression a good candidate for clinical use.

Digital medical atlases can contain anatomical information which is valuable for medical doctors in diagnosing and treating illnesses. The increased availability of such atlases has created an interest for computer algorithms which are capable of integrating such atlas information into patient specific dataprocessing. The field of medical image registration aim at calculating how to match one medical image to another. Here the atlas information could give important hints of which kinds of motion are plausible in different locations of the anatomy. Being able to incorporate such atlas specific information could potentially improve the matching of images and plausibility of image registration - ultimately providing a more correct information on which to base health care diagnosis and treatment decisions.In this licentiate thesis a generic signal processing framework is derived : Global Linear Optimization (GLO). The power of the GLO framework is first demonstrated quantitatively in a very high performing image denoiser. Important proofs of concepts are then made deriving and implementing three important capabilities regarding adaptive filtering of vector fields in medica limage registration:Global regularization with local anisotropic certainty metric.Allowing sliding motion along organ and tissue boundaries.Enforcing an incompressible motion in specific areas or volumes.In the three publications included in this thesis, the GLO framework is shown to be able to incorporate one each of these capabilities. In the third and final paper a demonstration is made how to integrate more and more of the capabilities above into the same GLO to perform adaptive processing on relevant clinical data. It is shown how each added capability improves the result of the image registration. In the end of the thesis there is a discussion which highlights the advantage of the contributions made as compared to previous methods in the scientific literature.

The software packages SPM, FSL and AFNI are the most widely used packages for the analysis of functional magnetic resonance imaging (fMRI) data. Despite this fact, the validity of the statistical methods has only been tested using simulated data. By analyzing resting state fMRI data (which should not contain specific forms of brain activity) from 396 healthy controls, we here show that all three software packages give inflated false positive rates (4%-96% compared to the expected 5%). We isolate the sources of these problems and find that SPM mainly suffers from a too simple noise model, while FSL underestimates the spatial smoothness. These results highlight the need of validating the statistical methods being used for fMRI.

We report a single-step procedure for growth of ohmic Ti3SiC2 on 4H-SiC by sputter-deposition of Ti at 960 degrees C, based on the Ti-SiC solid-state reaction during deposition. X-ray diffraction and electron microscopy show the growth of interfacial Ti3SiC2. The as-deposited contacts are ohmic, in contrast to multistep processes with deposition followed by rapid thermal annealing. This procedure also offers the possibility of direct synthesis of oxygen-barrier capping layers before exposure to air, potentially improving contact stability in high-temperature and high-power devices. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

High-temperature iridium-gated field effect transistors based on silicon carbide have been used for sensitive detection of specific volatile organic compounds (VOCs) in concentrations of health concern, for indoor air quality monitoring and control. Formaldehyde, naphthalene, and benzene were studied as hazardous VOCs at parts per billion (ppb) down to sub-ppb levels. The sensor performance and characteristics were investigated at a constant temperature of 330 °C and at different levels of relative humidity up to 60%, showing good stability and repeatability of the sensor response, and excellent detection limits in the sub-ppb range.