The functioning assessment short test (FAST): Clinically meaningful response threshold in patients with major depressive disorder receiving antidepressant treatment.

BACKGROUND: Functional impairment is common in patients with major depressive disorder (MDD). The Functioning Assessment Short Test (FAST) provides a detailed clinician-rated assessment of functioning across multiple aspects of daily life. This study aimed to establish clinically relevant response thresholds for the FAST in patients with MDD receiving antidepressant treatment. METHODS: Data were derived from three 8-week clinical trials of antidepressant therapy in patients with MDD that included assessment of functioning using the FAST as a pre-specified endpoint. The minimal clinically important difference (MCID) and threshold for response in terms of change in FAST total score were determined using anchor-based methods. RESULTS: After 8 weeks of antidepressant treatment, the mean reduction in FAST total score in patients considered clinically minimally improved (Clinical Global Impression-Improvement [CGII] score of 3) was 7-9 points (~20 % reduction). The threshold for functional response (reduction in FAST total score from baseline in patients with a CGI-I score of ≤2 at week 8) was 16-19 points (~50 % reduction). The threshold for functional response was higher in patients with MDD and comorbid generalized anxiety disorder than in those with MDD alone (mean reduction in FAST total score at 8 weeks: 26 points [63 %]). LIMITATIONS: Short-term studies. CONCLUSIONS: These results provide further validation of the FAST for assessing functioning in patients with MDD. In patients with MDD, the suggested MCID for FAST total score is 7-9 points and the proposed threshold for response is a reduction from baseline of approximately 50 %.

RF coil design strategies for improving SNR at the ultrahigh magnetic field of 10.5 Tesla.

Purpose: To develop multichannel transmit and receive arrays towards capturing the ultimate-intrinsic-SNR (uiSNR) at 10.5 Tesla (T) and to demonstrate the feasibility and potential of whole-brain, high-resolution human brain imaging at this high field strength. Methods: A dual row 16-channel self-decoupled transmit (Tx) array was converted to a 16Tx/Rx transceiver using custom transmit/receive switches. A 64-channel receive-only (64Rx) array was built to fit into the 16Tx/Rx array. Electromagnetic modeling and experiments were employed to define safe operation limits of the resulting 16Tx/80Rx array and obtain FDA approval for human use. Results: The 64Rx array alone captured approximately 50% of the central uiSNR at 10.5T while the identical 7T 64Rx array captured ∼76% of uiSNR at this lower field strength. The 16Tx/80Rx configuration brought the fraction of uiSNR captured at 10.5T to levels comparable to the performance of the 64Rx array at 7T. SNR data obtained at the two field strengths with these arrays displayed dependent increases over a large central region. Whole-brain high resolution T 2 * and T 1 weighted anatomical and gradient-recalled echo EPI BOLD fMRI images were obtained at 10.5T for the first time with such an advanced array, illustrating the promise of >10T fields in studying the human brain. Conclusion: We demonstrated the ability to approach the uiSNR at 10.5T over the human brain with a novel, high channel count array, achieving large SNR gains over 7T, currently the most commonly employed ultrahigh field platform, and demonstrate high resolution and high contrast anatomical and functional imaging at 10.5T.

Arduino-Based Readout Electronics for Nuclear and Particle Physics.

Open Hardware-based microcontrollers, especially the Arduino platform, have become a comparably easy-to-use tool for rapid prototyping and implementing creative solutions. Such devices in combination with dedicated front-end electronics can offer low-cost alternatives for student projects, slow control and independently operating small-scale instrumentation. The capabilities can be extended to data taking and signal analysis at mid-level rates. Two detector realizations are presented, which cover the readouts of proportional counter tubes and of scintillators or wavelength-shifting fibers with silicon photomultipliers (SiPMs). The SiPMTrigger realizes a small-scale design for coincidence readout of SiPMs as a trigger or veto detector. It consists of a custom mixed signal front-end board featuring signal amplification, discrimination and a coincidence unit for rates of up to 200 kHz. The nCatcher transforms an Arduino Nano to a proportional counter readout with pulse shape analysis: time over threshold measurement and a 10-bit analog-to-digital converter for pulse heights. The device is suitable for low-to-medium-rate environments up to 5 kHz, where a good signal-to-noise ratio is crucial. We showcase the monitoring of thermal neutrons. For data taking and slow control, a logger board is presented that features an SD card and GSM/LoRa interface.

Universal modes: Calibration-free time-interleaved acquisition of modes.

PURPOSE: To introduce universal modes by applying the universal pulse concept to time-interleaved acquisition of modes (TIAMO), thereby achieving calibration-free B 1 + $$ {B}_1^{+} $$ inhomogeneity mitigation for body imaging at ultra-high fields. METHODS: Two databases of different RF arrays were used to demonstrate the feasibility of universal modes. The first comprised 31 cardiac in vivo data sets acquired at 7T while the second consisted of 6 simulated 10.5T pelvic data sets. Subject-specific solutions and universal modes were computed and subsequently evaluated alongside predefined default modes. For the cardiac database, subdivision into subpopulations was investigated. The optimization was performed using least-squares (LS) TIAMO and acquisition modes optimized for refocused echoes (AMORE). Finally, universal modes based on simulated pelvis data were applied in vivo at 10.5T. RESULTS: In all studied cases, the universal modes yield improvements over the predefined default modes of up to 51% (cardiac) and 30% (pelvic) in terms of median excitation error when using two modes. The subpopulation-specific cardiac solutions revealed a further improvement of universal modes at the expense of increased errors when applied outside the appropriate subpopulation. Direct application of simulation-based universal modes in vivo resulted in up to a 14% reduction in excitation error compared to default modes and up to a 34% reduction in peak 10 g local specific absorption rate (SAR) compared to subject-specific solutions. CONCLUSIONS: Universal modes are feasible for calibration-free B 1 + $$ {B}_1^{+} $$ inhomogeneity mitigation at ultra-high fields. In addition, simulation-based solutions can be applied directly in vivo, eliminating the need for large in vivo databases.

Toward accurate and fast velocity quantification with 3D ultrashort TE phase-contrast imaging.

PURPOSE: Traditional phase-contrast MRI is affected by displacement artifacts caused by non-synchronized spatial- and velocity-encoding time points. The resulting inaccurate velocity maps can affect the accuracy of derived hemodynamic parameters. This study proposes and characterizes a 3D radial phase-contrast UTE (PC-UTE) sequence to reduce displacement artifacts. Furthermore, it investigates the displacement of a standard Cartesian flow sequence by utilizing a displacement-free synchronized-single-point-imaging MR sequence (SYNC-SPI) that requires clinically prohibitively long acquisition times. METHODS: 3D flow data was acquired at 3T at three different constant flow rates and varying spatial resolutions in a stenotic aorta phantom using the proposed PC-UTE, a Cartesian flow sequence, and a SYNC-SPI sequence as reference. Expected displacement artifacts were calculated from gradient timing waveforms and compared to displacement values measured in the in vitro flow experiments. RESULTS: The PC-UTE sequence reduces displacement and intravoxel dephasing, leading to decreased geometric distortions and signal cancellations in magnitude images, and more spatially accurate velocity quantification compared to the Cartesian flow acquisitions; errors increase with velocity and higher spatial resolution. CONCLUSION: PC-UTE MRI can measure velocity vector fields with greater accuracy than Cartesian acquisitions (although pulsatile fields were not studied) and shorter scan times than SYNC-SPI. As such, this approach is superior to traditional Cartesian 3D and 4D flow MRI when spatial misrepresentations cannot be tolerated, for example, when computational fluid dynamics simulations are compared to or combined with in vitro or in vivo measurements, or regional parameters such as wall shear stress are of interest.

Improved 1 H body imaging at 10.5 T: Validation and VOP-enabled imaging in vivo with a 16-channel transceiver dipole array.

PURPOSE: To increase the RF coil performance and RF management for body imaging at 10.5 T by validating and evaluating a high-density 16-channel transceiver array, implementing virtual observation points (VOPs), and demonstrating specific absorption rate (SAR) constrained imaging in vivo. METHODS: The inaccuracy of the electromagnetic model of the array was quantified based on B1 + and SAR data. Inter-subject variability was estimated using a new approach based on the relative SAR deviation of different RF shims between human body models. The pTx performance of the 16-channel array was assessed in simulation by comparison to a previously demonstrated 10-channel array. In vivo imaging of the prostate was performed demonstrating SAR-constrained static RF shimming and acquisition modes optimized for refocused echoes (AMORE). RESULTS: The model inaccuracy of 29% and the inter-subject variability of 85% resulted in a total safety factor of 1.91 for pelvis studies. For renal and cardiac imaging, inter-subject variabilities of 121% and 141% lead to total safety factors of 2.25 and 2.45, respectively. The shorter wavelength at 10.5 T supported the increased element density of the 16-channel array which in turn outperformed the 10-channel version for all investigated metrics. Peak 10 g local SAR reduction of more than 25% without a loss of image quality was achieved in vivo, allowing a theoretical improvement in measurement efficiency of up to 66%. CONCLUSIONS: By validating and characterizing a 16-channel dipole transceiver array, this work demonstrates, for the first time, a VOP-enabled RF coil for human torso imaging enabling increased pTx performance at 10.5 T.

Effectiveness of vortioxetine in patients with major depressive disorder and early-stage dementia: The MEMORY study.

BACKGROUND: Depression and dementia are highly prevalent in older adults and often co-occur. This Phase IV study investigated the effectiveness and tolerability of vortioxetine in improving depressive symptoms, cognitive performance, daily and global functioning and health-related quality of life (HRQoL) in patients with major depressive disorder (MDD) and comorbid early-stage dementia. METHODS: Patients (n = 82) aged 55-85 years with a primary diagnosis of MDD (onset before age 55 years) and comorbid early-stage dementia (diagnosed ≥6 months before screening and after onset of MDD; Mini-Mental State Examination-2 total score, 20-24) received vortioxetine for 12 weeks (initiated at 5 mg/day and up-titrated to 10 mg/day at day 8, with flexible dosing thereafter [5-20 mg/day]). The primary endpoint was change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 12. RESULTS: Significant improvement in depressive symptom severity was seen from week 1 onwards (P < 0.0001). At week 12, the least-square mean (standard error) change in MADRS total score from baseline was -12.4 (0.78). Significant improvements in cognitive performance were observed (from week 1 for the Digit Symbol Substitution Test and week 4 for the Rey Auditory Verbal Learning Test). Patients also experienced significant improvements in daily and global functioning, and HRQoL. Vortioxetine was well tolerated. From week 4 onwards, more than 50 % of patients were receiving 20 mg/day. LIMITATIONS: Open-label study. CONCLUSIONS: Vortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks. TRIAL REGISTRATION: ClinicalTrials.gov/ct2/show/NCT04294654.

Long-term safety and efficacy, including anhedonia, of vortioxetine for major depressive disorder: findings from two open-label studies.

OBJECTIVE: Evaluate the long-term safety and efficacy of vortioxetine in the management of major depressive disorder (MDD) in two open-label one-year studies, including a post-hoc analysis of its effects on symptoms related to anhedonia. METHODS: Both studies were 52-week, open-label, flexible-dose extension studies to evaluate the safety and efficacy of vortioxetine in adult patients with MDD following prior double-blind studies. Patients in the first study (NCT00761306) were flexibly treated with vortioxetine 5 or 10 mg/day (N = 74), and patients in the second study (NCT01323478) received vortioxetine 15 or 20 mg/day (N = 71). RESULTS: The safety and tolerability profile of vortioxetine was similar between the two studies; treatment-emergent adverse events with the highest incidence were nausea, dizziness, headache, and nasopharyngitis. Across both studies, improvements achieved during the preceding double-blind studies period were maintained, and additional improvements were observed with open-label treatment. Patients showed a mean ± SD reduction (improvement) in Montgomery and Åsberg Depression Rating Scale (MADRS) total score from open-label baseline to Week 52 of 4.3 ± 9.2 points in the 5-10 mg study, and 10.9 ± 10.0 in the 15-20 mg study. Post-hoc MMRM analyses of MADRS anhedonia factor scores also showed continued improvements over long-term treatment; patients showed a mean ± SE reduction from an open-label baseline to Week 52 of 3.10 ± 0.57 points in the 5-10 mg study, and 5.62 ± 0.60 in the 15-20 mg study. CONCLUSIONS: Data from both studies confirm the safety and efficacy of flexibly dosed vortioxetine over 52 weeks of treatment and demonstrate that MADRS anhedonia factor scores continue to improve with long-term maintenance treatment.

SO2 and copper tolerance exhibit an evolutionary trade-off in Saccharomyces cerevisiae.

Copper tolerance and SO2 tolerance are two well-studied phenotypic traits of Saccharomyces cerevisiae. The genetic bases of these traits are the allelic expansion at the CUP1 locus and reciprocal translocation at the SSU1 locus, respectively. Previous work identified a negative association between SO2 and copper tolerance in S. cerevisiae wine yeasts. Here we probe the relationship between SO2 and copper tolerance and show that an increase in CUP1 copy number does not always impart copper tolerance in S. cerevisiae wine yeast. Bulk-segregant QTL analysis was used to identify variance at SSU1 as a causative factor in copper sensitivity, which was verified by reciprocal hemizygosity analysis in a strain carrying 20 copies of CUP1. Transcriptional and proteomic analysis demonstrated that SSU1 over-expression did not suppress CUP1 transcription or constrain protein production and provided evidence that SSU1 over-expression induced sulfur limitation during exposure to copper. Finally, an SSU1 over-expressing strain exhibited increased sensitivity to moderately elevated copper concentrations in sulfur-limited medium, demonstrating that SSU1 over-expression burdens the sulfate assimilation pathway. Over-expression of MET 3/14/16, genes upstream of H2S production in the sulfate assimilation pathway increased the production of SO2 and H2S but did not improve copper sensitivity in an SSU1 over-expressing background. We conclude that copper and SO2 tolerance are conditional traits in S. cerevisiae and provide evidence of the metabolic basis for their mutual exclusivity. These findings suggest an evolutionary driver for the extreme amplification of CUP1 observed in some yeasts.

Improved TSE imaging at ultrahigh field using nonlocalized efficiency RF shimming and acquisition modes optimized for refocused echoes (AMORE).

PURPOSE: To develop and evaluate a novel RF shimming optimization strategy tailored to improve the transmit efficiency in turbo spin echo imaging when performing time-interleaved acquisition of modes (TIAMO) at ultrahigh fields. THEORY AND METHODS: A nonlocalized efficiency shimming cost function is proposed and extended to perform TIAMO using acquisition modes optimized for refocused echoes (AMORE). The nonlocalized efficiency shimming was demonstrated in brain and knee imaging at 7 Tesla. Phantom and in vivo torso imaging studies were performed to compare the performance between AMORE and previously proposed TIAMO mode optimizations with and without localized constraints in turbo spin echo and gradient echo acquisitions. RESULTS: The proposed nonlocalized efficiency RF shimming produced a circularly polarized-like field with fewer signal dropouts in the brain and knee. For larger targets, AMORE was used and required a significantly lower transmitter voltage to produce a similar contrast to existing TIAMO mode design approaches for turbo spin echo as well as gradient echo acquisitions. In vivo, AMORE effectively reduced signal dropout in the interior torso while providing more uniform contrast with reduced transmit power. A local constraint further improved performance for a target region while maintaining performance in the larger FOV. CONCLUSION: AMORE based on the presented nonlocalized efficiency shimming cost function demonstrated improved contrast and SNR uniformity as well as increased transmit efficiency for both gradient echo and turbo spin echo acquisitions.

Efficacy and safety of vortioxetine in treatment of patients with major depressive disorder and common co-morbid physical illness.

BACKGROUND: The multimodal antidepressant vortioxetine is effective in reducing somatic symptoms in patients with major depressive disorder (MDD), but little is known about its effects in reducing depressive symptoms in patients with common comorbid physical illnesses. METHODS: This was a pooled analysis of 13 randomized, placebo-controlled trials which evaluated the efficacy (using the Montgomery-Åsberg Depression Rating Scale [MADRS]) and safety of vortioxetine (5-20 mg/day) in adult patients with MDD. We evaluated stable somatic comorbid conditions that were verified by a diagnosis and had sufficient database representation. RESULTS: Of the 5982 patients included in the database, 963 (16.1%) patients had a diagnosis of cardiovascular disease, 152 (2.5%) had diabetes mellitus and 26 (0.4%) had chronic obstructive pulmonary disorder (COPD). At Week 8, adjusted mean[95%CI] treatment differences (vortioxetine vs. placebo) on MADRS total scores were -2.7[-4.2, -1.3] (p = 0.0002) points for the cardiovascular disease, -4.0[-7.7, -0.4] (p = 0.03) for the diabetes, and -6.2[-21.3, 8.9] (p = 0.36) for the COPD groups. The rate and pattern of adverse events were similar across the sub-groups with comorbidities and was consistent with that expected for vortioxetine treatment. LIMITATIONS: The primary studies were not designed to investigate the relationship between vortioxetine and comorbidities, nor were the post hoc analyses powered to detect group differences. CONCLUSIONS: Patients with MDD and comorbid cardiovascular disease or diabetes respond to vortioxetine in a similar way to the broader MDD population. Vortioxetine was generally safe and well tolerated and without unexpected adverse events in these subpopulations, most of whom are taking multiple concomitant medications.

On-the-Fly Mass Spectrometry in Digital Microfluidics Enabled by a Microspray Hole: Toward Multidimensional Reaction Monitoring in Automated Synthesis Platforms.

We report an approach for the online coupling of digital microfluidics (DMF) with mass spectrometry (MS) using a chip-integrated microspray hole (µSH). The technique uses an adapted electrostatic spray ionization (ESTASI) method to spray a portion of a sample droplet through a microhole in the cover plate, allowing its chemical content to be analyzed by MS. This eliminates the need for chip disassembly or the introduction of capillary emitters for MS analysis, as required by state-of-the-art. For the first time, this allows the essential advantage of a DMF device─free droplet movement─to be retained during MS analysis. The broad applicability of the developed seamless coupling of DMF and mass spectrometry was successfully applied to the study of various on-chip organic syntheses as well as protein and peptide analysis. In the case of a Hantzsch synthesis, we were able to show that the method is very well suited for monitoring even rapid chemical reactions that are completed in a few seconds. In addition, the strength of the low resource consumption in such on-chip microsyntheses was demonstrated by the example of enzymatic brominations, for which only a minute amount of a special haloperoxidase is required in the droplet. The unique selling point of this approach is that the analyzed droplet remains completely movable after the MS measurement and is available for subsequent on-DMF chip processes. This is illustrated here for the example of MS analysis of the starting materials in the corresponding droplets before they are combined to investigate the reaction progress by DMF-MS further. This technology enables the ongoing and almost unlimited tracking of multistep chemical processes in a DMF chip and offers exciting prospects for transforming digital microfluidics into automated synthesis platforms.

Iterative metal artifact reduction on a clinical photon counting system-technical possibilities and reconstruction selection for optimal results dependent on the metal scenario.

Objective.To give an overview about technical possibilities for metal artifact reduction of the first clinical photon-counting CT system and assess optimal reconstruction settings in a phantom study, assessing monoenergetic imaging (VMI) and iterative metal artifact reduction (iMAR).Approach.Scans were performed with 120 kV and Sn140 kV on the first clinical photon-counting detector CT scanner. To quantify artifact reduction, anthropomorphic phantoms (hip, dental, spine, neuro) were assessed, in addition to a tissue characterization phantom (Gammex) to quantify the HU restoration accuracy, all with removable metal inserts. Each setup was reconstructed with and without dedicated iMAR, and VMIs were computed in 10 keV steps from 40 keV (60 keV at Sn140 kV) to 190 keV for all setups (ground truth and metal with and without iMAR). To find the optimal energy, pixel-wise errors were computed in relevant ROIs in water-equivalent tissue around the metal in each phantom setup. To assess HU restoration potential, measurements were performed in the Gammex phantom's inserts.Main results.Large metal objects (hip head) or metal with high atomic numbers (dental and neuro) do not benefit from higher-energetic reconstructions. The hip shaft (large, low atomic number) comprises a lower base artifact level than the head, still without an energetic optimum. Within the spine (short penetration length, low atomic number) an energy optimum could be identified for both spectra (100 keV for 120 kV and 120 keV for Sn140 kV). The Gammex showed best HU restoration at 100 keV for 120 kV and at 110 keV for Sn140 kV. In all cases, additional iMAR reduced the base artifact level.Significance.This study shows that a novel photon-counting CT system has the capability to reduce metal artifacts in metal types with low atomic number and low penetration length by applying VMI. For all other metal types, additional iMAR is required to reduce artifacts.

Effectiveness of vortioxetine in patients with major depressive disorder comorbid with generalized anxiety disorder: Results of the RECONNECT study.

BACKGROUND: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are frequently comorbid. AIMS: To assess the effectiveness of vortioxetine in patients with MDD and comorbid GAD. METHODS: Open-label, 8-week study (NCT04220996) in 100 adult outpatients with severe MDD and severe comorbid GAD receiving vortioxetine as first treatment for the current depressive episode or switching to vortioxetine due to inadequate response to another drug for depression. Vortioxetine starting dosage was 10 mg/day, with forced up-titration to 20 mg/day after 1 week. Response was defined as ⩾50% decrease in Montgomery-Åsberg Depression Rating Scale (MADRS) and/or Hamilton Anxiety Rating Scale (HAM-A) total score from baseline; remission defined as MADRS and/or HAM-A total score ⩽10. RESULTS: Clinically meaningful and statistically significant improvements from baseline in symptoms of depression and anxiety, and overall functioning and health-related quality of life, were observed after 8 weeks' vortioxetine treatment (all changes p < 0.0001 vs baseline). At week 8, rates of MADRS response and remission were 61% and 35%, respectively. Corresponding rates of HAM-A response and remission were 55% and 42%. Response on both the MADRS and HAM-A scales was achieved by 52% of patients; 31% achieved remission on both scales. Vortioxetine dose up-titration was well tolerated; no unexpected adverse events were reported. CONCLUSION: Vortioxetine demonstrates effectiveness in significantly reducing symptoms of both depression and anxiety in patients with severe MDD comorbid with severe GAD. Findings support increasing vortioxetine dosage to 20 mg/day early in the course of therapy, and show that this may be achieved without compromising tolerability.

Vortioxetine for Major Depressive Disorder in Adolescents: 12-Week Randomized, Placebo-Controlled, Fluoxetine-Referenced, Fixed-Dose Study.

OBJECTIVE: To evaluate the efficacy and safety of vortioxetine in adolescents with major depressive disorder (MDD). METHOD: After 4 weeks of single-blind lead-in treatment with a Brief Psychosocial Intervention (BPI) plus placebo, patients (aged 12-17 years) with MDD (DSM-5) who did not meet response criteria (Children's Depression Rating Scale-Revised [CDRS-R]; total score ≥40 plus <40% reduction and a Parent Global Assessment score >2) were randomized 1:1:1:1 to 8 weeks of BPI plus double-blind treatment with vortioxetine 10 mg, vortioxetine 20 mg, fluoxetine 20 mg, or placebo. The primary endpoint was change from randomization in CDRS-R total score at week 8; the primary comparison was the average effect of 2 vortioxetine doses vs placebo. RESULTS: Of 784 patients enrolled in the lead-in, 616 were randomized. At week 8, the mean change in CDRS-R total score averaged for vortioxetine doses was -18.01 (SE = 0.98) and the mean difference vs placebo was 0.21 (P = .878; not significant). For fluoxetine, the mean change in CDRS-R total score was -21.95 and the mean difference vs placebo was -3.73 (P = .015). Treatment-emergent adverse events occurring in ≥5% of patients in either vortioxetine arm and at least twice more frequently than placebo were nausea, headache, vomiting, and dizziness. CONCLUSION: Patients in all groups showed reduction in CDRS-R scores by the end of the study, with no difference between combined doses of vortioxetine and placebo. The primary endpoint was not met, thereby rendering the study negative. The overall favorable safety profile of vortioxetine in an adolescent patient population was consistent with that seen in adults. CLINICAL TRIAL REGISTRATION INFORMATION: Active Reference (Fluoxetine) Fixed-Dose Study of Vortioxetine in Paediatric Patients Aged 12 to 17 Years With Major Depressive Disorder (MDD); http://clinicaltrials.gov; NCT02709746.

Performance and safety assessment of an integrated transmit array for body imaging at 7 T under consideration of specific absorption rate, tissue temperature, and thermal dose.

In this study, the performance of an integrated body-imaging array for 7 T with 32 radiofrequency (RF) channels under consideration of local specific absorption rate (SAR), tissue temperature, and thermal dose limits was evaluated and the imaging performance was compared with a clinical 3 T body coil. Thirty-two transmit elements were placed in three rings between the bore liner and RF shield of the gradient coil. Slice-selective RF pulse optimizations for B1 shimming and spokes were performed for differently oriented slices in the body under consideration of realistic constraints for power and local SAR. To improve the B1+ homogeneity, safety assessments based on temperature and thermal dose were performed to possibly allow for higher input power for the pulse optimization than permissible with SAR limits. The results showed that using two spokes, the 7 T array outperformed the 3 T birdcage in all the considered regions of interest. However, a significantly higher SAR or lower duty cycle at 7 T is necessary in some cases to achieve similar B1+ homogeneity as at 3 T. The homogeneity in up to 50 cm-long coronal slices can particularly benefit from the high RF shim performance provided by the 32 RF channels. The thermal dose approach increases the allowable input power and the corresponding local SAR, in one example up to 100 W/kg, without limiting the exposure time necessary for an MR examination. In conclusion, the integrated antenna array at 7 T enables a clinical workflow for body imaging and comparable imaging performance to a conventional 3 T clinical body coil.

A Sensor Fault Detection Scheme as a Functional Safety Feature for DC-DC Converters.

DC-DC converters are widely used in a large number of power conversion applications. As in many other systems, they are designed to automatically prevent dangerous failures or control them when they arise; this is called functional safety. Therefore, random hardware failures such as sensor faults have to be detected and handled properly. This proper handling means achieving or maintaining a safe state according to ISO 26262. However, to achieve or maintain a safe state, a fault has to be detected first. Sensor faults within DC-DC converters are generally detected with hardware-redundant sensors, despite all their drawbacks. Within this article, this redundancy is addressed using observer-based techniques utilizing Extended Kalman Filters (EKFs). Moreover, the paper proposes a fault detection and isolation scheme to guarantee functional safety. For this, a cross-EKF structure is implemented to work in cross-parallel to the real sensors and to replace the sensors in case of a fault. This ensures the continuity of the service in case of sensor faults. This idea is based on the concept of the virtual sensor which replaces the sensor in case of fault. Moreover, the concept of the virtual sensor is broader. In fact, if a system is observable, the observer offers a better performance than the sensor. In this context, this paper gives a contribution in this area. The effectiveness of this approach is tested with measurements on a buck converter prototype.

Analysis of Transcriptomic Response to SO2 by Oenococcus oeni Growing in Continuous Culture.

To successfully complete malolactic fermentation (MLF), Oenococcus oeni must overcome wine stress conditions of low pH, high ethanol, and the presence of SO2. Failure to complete MLF may result in detrimental effects to the quality and stability of the resulting wines. Research efforts to date have focused on elucidating the mechanisms and genetic features that confer the ability to withstand low pH and high ethanol concentrations on O. oeni; however, the responses to SO2 stress are less well defined. This study focused on characterizing the transcriptional response of O. oeni to SO2 challenge during cultivation in a continuous system at wine-like pH (3.5). This experimental design allowed the precise discrimination of transcriptional changes linked to SO2 stress from responses associated with growth stage and cultivation parameters. Differential gene expression analysis revealed major transcriptional changes following SO2 exposure and suggested that this compound primarily interacts with intracellular proteins, DNA, and the cell envelope of O. oeni. The molecular chaperone hsp20, which has a demonstrated function in the heat, ethanol, and acid stress response, was highly upregulated, confirming its additional role in the response of this species to SO2 stress. This work also reports the first nanopore-based complete genome assemblies for O. oeni. IMPORTANCE Malolactic fermentation is an indispensable step in the elaboration of most wines and is generally performed by Oenococcus oeni, a Gram-positive heterofermentative lactic acid bacterium species. While O. oeni is tolerant to many of the wine stresses, including low pH and high ethanol concentrations, it has high sensitivity to SO2, an antiseptic and antioxidant compound regularly used in winemaking. Understanding the physiological changes induced in O. oeni by SO2 stress is essential for the development of more robust starter cultures and methods for their use. This study describes the main transcriptional changes induced by SO2 stress in the wine bacterium O. oeni and provides foundational understanding on how this compound interacts with the cellular components and the induced protective mechanisms of this species.

Aromatic Higher Alcohols in Wine: Implication on Aroma and Palate Attributes during Chardonnay Aging.

The higher alcohols 2-phenylethanol, tryptophol, and tyrosol are a group of yeast-derived compounds that have been shown to affect the aroma and flavour of fermented beverages. Five variants of the industrial wine strain AWRI796, previously isolated due to their elevated production of the 'rose-like aroma' compound 2-phenylethanol, were characterised during pilot-scale fermentation of a Chardonnay juice. We show that these variants not only increase the concentration of 2-phenylethanol but also modulate the formation of the higher alcohols tryptophol, tyrosol, and methionol, as well as other volatile sulfur compounds derived from methionine, highlighting the connections between yeast nitrogen and sulfur metabolism during fermentation. We also investigate the development of these compounds during wine storage, focusing on the sulfonation of tryptophol. Finally, the sensory properties of wines produced using these strains were quantified at two time points, unravelling differences produced by biologically modulating higher alcohols and the dynamic changes in wine flavour over aging.

Configurable Sensor Model Architecture for the Development of Automated Driving Systems.

Sensor models provide the required environmental perception information for the development and testing of automated driving systems in virtual vehicle environments. In this article, a configurable sensor model architecture is introduced. Based on methods of model-based systems engineering (MBSE) and functional decomposition, this approach supports a flexible and continuous way to use sensor models in automotive development. Modeled sensor effects, representing single-sensor properties, are combined to an overall sensor behavior. This improves reusability and enables adaptation to specific requirements of the development. Finally, a first practical application of the configurable sensor model architecture is demonstrated, using two exemplary sensor effects: the geometric field of view (FoV) and the object-dependent FoV.