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IntroductionIdentifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials.MethodsSerial T1-weighted magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point.ResultsAtrophy increased after the change-point, which occurred 1-1.5 years (assuming a single step change in atrophy rate) or 3-8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change-point.DiscussionAtrophy rates are pathologically increased up to seven years before "expected onset". During this period, atrophy rates may be useful for inclusion and tracking of disease progression.

The practice of spiritual care in health has included the goal of addressing the spiritual needs of healthcare staff. Spiritual-care practitioners have had some difficulty in fulfilling this goal, which has created the need for innovative approaches. Two approaches designed to address the spiritual and existential needs of staff are Value-Based Reflective Practice (VBRP) and Schwartz Rounds. Schwartz Rounds are a regular whole-hospital meeting where staff are invited to share and discuss the social and emotional aspects of their work. They are an evidence-based intervention to reduce psychological distress and improve staff wellbeing. This paper seeks to explore the role of spiritual care practitioners in addressing the spiritual and existential needs of staff. It then explores the synergy of these roles with the theory and practice of the above approaches, with a particular emphasis on Schwartz Rounds. The paper is grounded in the experience of the authors collaborating to establish Schwartz Rounds in a large and culturally diverse hospital while also playing a leadership role in the establishment and sustainability of Schwartz programmes in other settings. [ABSTRACT FROM AUTHOR]

IntroductionAlzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders.MethodsWe review the contributions of the MRI core from present and past cycles of ADNI (ADNI-1, -Grand Opportunity and -2). We also review plans for the future-ADNI-3.ResultsContributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials.DiscussionOver the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future.

Stable MR acquisition is essential for reliable measurement of brain atrophy in longitudinal studies. One attractive recent advance in MRI is to speed up acquisition using parallel imaging (e.g. reducing volumetric T1-weighted acquisition scan times from around 9 to 5 min). In some studies, a decision to change to an accelerated acquisition may have been deliberately taken, while in others repeat scans may occasionally be accidentally acquired with an accelerated acquisition. In ADNI, non-accelerated and accelerated scans were acquired in the same scanning session on each individual. We investigated the impact on brain atrophy as measured by k-means normalized boundary shift integral (KN-BSI) and deformation-based morphometry when changing from non-accelerated to accelerated MRI acquisitions over a 12-month interval using scans of 422 subjects from ADNI. KN-BSIs were calculated using both a non-accelerated baseline scan and non-accelerated 12-month scans (i.e. consistent acquisition), and a non-accelerated baseline scan and an accelerated 12-month scan (i.e. changed acquisition). Fluid-based non-rigid registration was also performed on those scans to estimate the brain atrophy rate. We found that the effect on KN-BSI and fluid-based non-rigid registration depended on the scanner manufacturer. For KN-BSI, in Philips and Siemens scanners, the change had very little impact on the measured atrophy rate (increase of 0.051% in Philips and -0.035% in Siemens from consistent acquisition to changed acquisition), whereas, in GE, the change caused a mean reduction of 0.65% in the brain atrophy rate. This is likely due to the difference in tissue contrast between gray matter and cerebrospinal fluid in the non-accelerated and accelerated scans in GE, which uses IR-FSPGR instead of MP-RAGE. For fluid-based non-rigid registration, the change caused a mean increase of 0.29% in the brain atrophy rate in the changed acquisition compared with consistent acquisition in Philips, whereas in GE and Siemens, the change had less impact on the mean atrophy rate (increase of 0.18% in GE and 0.049% in Siemens). Moving from non-accelerated baseline scans to accelerated scans for follow-up may have surprisingly little effect on computed atrophy rates depending on the exact sequence details and the scanner manufacturer; even accidentally inconsistent scans of this nature may still be useful.

Modern computational neuroscience employs diverse software tools and multidisciplinary expertise to analyze heterogeneous brain data. The classical problems of gathering meaningful data, fitting specific models, and discovering appropriate analysis and visualization tools give way to a new class of computational challenges--management of large and incongruous data, integration and interoperability of computational resources, and data provenance. We designed, implemented and validated a new paradigm for addressing these challenges in the neuroimaging field. Our solution is based on the LONI Pipeline environment [3], [4], a graphical workflow environment for constructing and executing complex data processing protocols. We developed study-design, database and visual language programming functionalities within the LONI Pipeline that enable the construction of complete, elaborate and robust graphical workflows for analyzing neuroimaging and other data. These workflows facilitate open sharing and communication of data and metadata, concrete processing protocols, result validation, and study replication among different investigators and research groups. The LONI Pipeline features include distributed grid-enabled infrastructure, virtualized execution environment, efficient integration, data provenance, validation and distribution of new computational tools, automated data format conversion, and an intuitive graphical user interface. We demonstrate the new LONI Pipeline features using large scale neuroimaging studies based on data from the International Consortium for Brain Mapping [5] and the Alzheimer's Disease Neuroimaging Initiative [6]. User guides, forums, instructions and downloads of the LONI Pipeline environment are available at http://pipeline.loni.ucla.edu.

The practicalities of structural fatigue testing limit the fidelity of the cyclic load history that can be applied to a test structure. Testing is, therefore, a compromise between fatigue damage fidelity and test economy. A new methodology is proposed for multiaxial loading spectrum editing to extract cycles that contribute negligible damage during fatigue crack initiation. The method is based on projection by projection (PbP) technique and wavelet transform analysis (WTA) procedure. In this approach, the cycles with negligible contribution to damage in every decoupled projected loading path (i.e. obtained from PbP approach) are extracted using the WTA procedure. Each extracted segment is then replaced with an equivalent cycle that produces the same amount of damage. The effectiveness of the edited spectrums is evaluated by the degree of fatigue damage retention as the original damage and preservation of statistical parameter values. As a case study, the proposed approach has been applied to the numerically produced random bending-torsion fatigue spectrum in plane-stress condition. The result shows an average of 75% reduction of the original spectrums with retention of 90% of the original spectrums’ damage values.

Controllable in situ formation of nanoclusters with discrete active sites is highly desirable in heterogeneous catalysis. Herein, a titanium oxide-based Fenton-like catalyst is constructed using exfoliated Ti3C2 MXene as a template. Theoretical calculations reveal that a redox reaction between the surface Ti-deficit vacancies of the exfoliated Ti3C2 MXene and H2O2 molecules facilitates the in situ conversion of surface defects into titanium oxide nanoclusters anchoring on amorphous carbon (TiOx@C). The presence of mixed-valence Tid+ (d = 0, 2, 3, and 4) within TiOx@C is confirmed by X-ray photoelectron spectroscopy (XPS) and X-ray absorption fine structure (XAFS) characterizations. The abundant surface defects within TiOx@C effectively promote the generation of reactive oxygen species (ROS) leading to superior and stable Fenton-like catalytic degradation of atrazine, a typical agricultural herbicide. Such an in situ construction of Fenton-like catalysts through defect engineering also applies to other MXene family materials, such as V2C and Nb2C. [ABSTRACT FROM AUTHOR]

A high-order switching surface for boundary control of inverters is presented in this paper. The concept is based on using the natural response of the power stage to formulate a logarithmic function to approximate the ideal switching surface. With the proposed control method, the inverter exhibits better dynamic responses than the ones with the first-order or recently proposed second-order switching surfaces. It will also be shown that the first-order and second-order switching surfaces are the low-order approximations of high-order switching surface. As the high-order switching surface is close to the ideal switching surface, its high trajectory velocity along the switching surface makes the inverter state trajectory move toward the steady-state operating point in two switching actions under large-signal disturbances. The effects of the parametric variations on the output voltage and the large-signal characteristics of the inverter will be discussed. The proposed control method has been successfully applied to a 300-W, ll0-V, 60-Hz, single-phase full-bridge inverter. The steady-state and large-signal dynamic behaviors of the inverter supplying to resistive, nonlinear inductive, and full-wave rectifier loads will be given. Index Terms--Boundary control, dc-ac converter, inverters, nonlinear control.

A performance comparison of boundary control with the first- ([[sigma].sup.1]) and second-order ([[sigma].sup.2]) switching surfaces for buck converters operating in discontinuous conduction mode (DCM) is presented in this paper. Performance attributes under investigation include the average output voltage, output ripple voltage, switching frequency, parametric sensitivities to the component values, and large signal characteristics. Due to the presence of the output hysteresis band, an additional switching boundary formed by the zero-inductor-current trajectory is created. This phenomenon causes a shift of the operating point in converters with [[sigma]sup.1]. Conversely, the operating point remains unchanged in converters with [[sigma].sup.2]. As well as in continuous conduction mode (CCM), [[sigma].sup.2] can make the converter revert to the steady-state in two switching actions in DCM and gives better static and dynamic responses than [[sigma].sup.1] in both CCM and DCM. Most importantly, its control law and settings are applicable for both modes. Experimental results of a prototype are found to be in good agreement with theoretical predictions. Index Terms--Boundary control, geometric control method, first-order switching surface, second-order switching surface, state trajectory control.

Recent innovations in drug therapies have made it highly desirable to obtain sensitive biomarkers of disease progression that can be used to quantify the performance of candidate disease modifying drugs. In order to measure potential image-based biomarkers of disease progression in an experimental model of rheumatoid arthritis (RA), we present two different methods to automatically quantify changes in a bone in in-vivo serial magnetic resonance (MR) images from the model. Both methods are based on rigid and nonrigid image registration to perform the analysis. The first method uses segmentation propagation to delineate a bone from the serial MR images giving a global measure of temporal changes in bone volume. The second method uses rigid body registration to determine intensity change within a bone, and then maps these into a reference coordinate system using nonrigid registration. This gives a local measure of temporal changes in bone lesion volume. We detected significant temporal changes in local bone lesion volume in five out of eight identified candidate bone lesion regions, and significant difference in local bone lesion volume between male and female subjects in three out of eight candidate bone lesion regions. But the global bone volume was found to be fluctuating over time. Finally, we compare our findings with histology of the subjects and the manual segmentation of bone lesions. Index Terms--Histology, image analysis, magnetic resonance imaging (MRI), rheumatoid arthritis (RA).

A dynamic hysteresis control of the buck converter for achieving high slew-rate response to disturbances is proposed. The hysteresis band is derived from the output capacitor current that predicts the output voltage magnitude after a hypothesized switching action. Four switching criteria are formulated to dictate the state of the main switch. The output voltage can revert to the steady state in two switching actions after a large-signal disturbance. The technique is verified with the experimental results of a 50 W buck converter. Index Terms--Boundary control, DC-DC power conversion, large-signal stability, state trajectory prediction.