3-d residual eddy current field characterisation: applied to diffusion weighted magnetic resonance imaging.

Clinical use of the Stejskal-Tanner diffusion weighted images is hampered by the geometric distortions that result from the large residual 3-D eddy current field induced. In this work, we aimed to predict, using linear response theory, the residual 3-D eddy current field required for geometric distortion correction based on phantom eddy current field measurements. The predicted 3-D eddy current field induced by the diffusion-weighting gradients was able to reduce the root mean square error of the residual eddy current field to ~1 Hz. The model's performance was tested on diffusion weighted images of four normal volunteers, following distortion correction, the quality of the Stejskal-Tanner diffusion-weighted images was found to have comparable quality to image registration based corrections (FSL) at low b-values. Unlike registration techniques the correction was not hindered by low SNR at high b-values, and results in improved image quality relative to FSL. Characterization of the 3-D eddy current field with linear response theory enables the prediction of the 3-D eddy current field required to correct eddy current induced geometric distortions for a wide range of clinical and high b-value protocols.

Effective size of two feral domestic cat populations (Felis catus L): effect of the mating system.

A variety of behavioural traits have substantial effects on the gene dynamics and genetic structure of local populations. The mating system is a plastic trait that varies with environmental conditions in the domestic cat (Felis catus) allowing an intraspecific comparison of the impact of this feature on genetic characteristics of the population. To assess the potential effect of the heterogenity of males' contribution to the next generation on variance effective size, we applied the ecological approach of Nunney & Elam (1994) based upon a demographic and behavioural study, and the genetic 'temporal methods' of Waples (1989) and Berthier et al. (2002) using microsatellite markers. The two cat populations studied were nearly closed, similar in size and survival parameters, but differed in their mating system. Immigration appeared extremely restricted in both cases due to environmental and social constraints. As expected, the ratio of effective size to census number (Ne/N) was higher in the promiscuous cat population (harmonic mean = 42%) than in the polygynous one (33%), when Ne was calculated from the ecological method. Only the genetic results based on Waples' estimator were consistent with the ecological results, but failed to evidence an effect of the mating system. Results based on the estimation of Berthier et al. (2002) were extremely variable, with Ne sometimes exceeding census size. Such low reliability in the genetic results should retain attention for conservation purposes.

Eddy current effects on a clinical 7T-68 cm bore scanner.

INTRODUCTION: Eddy currents induced by switching of magnetic field gradients can lead to distortions in short echo-time spectroscopy or diffusion weighted imaging. In small bore magnets, such as human head-only systems, minimization of eddy current effects is more demanding because of the proximity of the gradient coil to conducting structures. METHODS: In the present study, the eddy current behavior achievable on a recently installed 7 tesla-68 cm bore head-only magnet was characterized. RESULTS: Residual effects after compensation were shown to be on the same order of magnitude as those measured on two whole body systems (3 and 4.7 T), while using two to three fold increased gradient slewrates.

Validation study of the French version of the observer-rater scales measuring coping and cognitive errors (CE-CAP) on a non-clinical population

This study examined the validity and reliability of the French version of two observer-rated measures developed to assess cognitive errors (cognitive errors rating system [CERS]) [6] and coping action patterns (coping action patterns rating system [CAPRS]) [22,24]. The CE measures 14 cognitive errors, broken down according to their valence positive or negative (see the definitions by A.T. Beck), and the CAP measures 12 coping categories, based on an comprehensive review literature, each broken down into three levels of action (affective, behavioural, cognitive). Thirty (N = 30) subjects recruited in a community sample participated in the study. They were interviewed according to a standardized clinical protocol: these interviews were transcribed and analysed with both observer-rated systems. Results showed that the inter-rater reliability of the two measures is good and that their internal validity is satisfactory, due to a non-significant canonical correlation between CAP and CE. With regard to discriminant validity, we found a non-significant canonical correlation between CAPRS and CISS, one of most widely used self-report questionnaire measuring coping. The same can be said for the correlation with a self-report questionnaire measuring symptoms (SCL-90-R). These results confirm the absence of confounds in the assessment of cognitive errors and of coping as assessed by these observer-rated scales and add an argument in favour of the French validation of the CE-CAP rating scales. (C) 2010 Elsevier Masson SAS. All rights reserved.

Functional dynamics of PDZ binding domains: a normal-mode analysis.

Postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains are relatively small (80-120 residues) protein binding modules central in the organization of receptor clusters and in the association of cellular proteins. Their main function is to bind C-terminals of selected proteins that are recognized through specific amino acids in their carboxyl end. Binding is associated with a deformation of the PDZ native structure and is responsible for dynamical changes in regions not in direct contact with the target. We investigate how this deformation is related to the harmonic dynamics of the PDZ structure and show that one low-frequency collective normal mode, characterized by the concerted movements of different secondary structures, is involved in the binding process. Our results suggest that even minimal structural changes are responsible for communication between distant regions of the protein, in agreement with recent NMR experiments. Thus, PDZ domains are a very clear example of how collective normal modes are able to characterize the relation between function and dynamics of proteins, and to provide indications on the precursors of binding/unbinding events.

Multimodal Highlighting of Structural Abnormalities in Diabetic Rat and Human Corneas.

PURPOSE: This study aimed to highlight structural corneal changes in a model of type 2 diabetes, using in vivo corneal confocal microscopy (CCM). The abnormalities were also characterized by transmission electron microscopy (TEM) and second harmonic generation (SHG) microscopy in rat and human corneas. METHODS: Goto-Kakizaki (GK) rats were observed at age 12 weeks (n = 3) and 1 year (n = 6), and compared to age-matched controls. After in vivo CCM examination, TEM and SHG microscopy were used to characterize the ultrastructure and the three-dimensional organization of the abnormalities. Human corneas from diabetic (n = 3) and nondiabetic (n = 3) patients were also included in the study. RESULTS: In the basal epithelium of GK rats, CCM revealed focal hyper-reflective areas, and histology showed proliferative cells with irregular basement membrane. In the anterior stroma, extracellular matrix modifications were detected by CCM and confirmed in histology. In the Descemet's membrane periphery of all the diabetic corneas, hyper-reflective deposits were highlighted using CCM and characterized as long-spacing collagen fibrils by TEM. SHG microscopy revealed these deposits with high contrast, allowing specific detection in diabetic human and rat corneas without preparation and characterization of their three-dimensional organization. CONCLUSION: Pathologic findings were observed early in the development of diabetes in GK rats. Similar abnormalities have been found in corneas from diabetic patients. TRANSLATIONAL RELEVANCE: This multidisciplinary study highlights diabetes-induced corneal abnormalities in an animal model, but also in diabetic donors. This could constitute a potential early marker for diagnosis of hyperglycemia-induced tissue changes.

Myocardial infarct size and mortality depend on the time of day-a large multicenter study.

BACKGROUND: Different studies have shown circadian variation of ischemic burden among patients with ST-Elevation Myocardial Infarction (STEMI), but with controversial results. The aim of this study was to analyze circadian variation of myocardial infarction size and in-hospital mortality in a large multicenter registry. METHODS: This retrospective, registry-based study was based on data from AMIS Plus, a large multicenter Swiss registry of patients who suffered myocardial infarction between 1999 and 2013. Peak creatine kinase (CK) was used as a proxy measure for myocardial infarction size. Associations between peak CK, in-hospital mortality, and the time of day at symptom onset were modelled using polynomial-harmonic regression methods. RESULTS: 6,223 STEMI patients were admitted to 82 acute-care hospitals in Switzerland and treated with primary angioplasty within six hours of symptom onset. Only the 24-hour harmonic was significantly associated with peak CK (p = 0.0001). The maximum average peak CK value (2,315 U/L) was for patients with symptom onset at 23:00, whereas the minimum average (2,017 U/L) was for onset at 11:00. The amplitude of variation was 298 U/L. In addition, no correlation was observed between ischemic time and circadian peak CK variation. Of the 6,223 patients, 223 (3.58%) died during index hospitalization. Remarkably, only the 24-hour harmonic was significantly associated with in-hospital mortality. The risk of death from STEMI was highest for patients with symptom onset at 00:00 and lowest for those with onset at 12:00. DISCUSSION: As a part of this first large study of STEMI patients treated with primary angioplasty in Swiss hospitals, investigations confirmed a circadian pattern to both peak CK and in-hospital mortality which were independent of total ischemic time. Accordingly, this study proposes that symptom onset time be incorporated as a prognosis factor in patients with myocardial infarction.

Positive contrast visualization of iron oxide-labeled stem cells using inversion-recovery with ON-resonant water suppression (IRON)

In proton magnetic resonance imaging (MRI) metallic substances lead to magnetic field distortions that often result in signal voids in the adjacent anatomic structures. Thus, metallic objects and superparamagnetic iron oxide (SPIO)-labeled cells appear as hypointense artifacts that obscure the underlying anatomy. The ability to illuminate these structures with positive contrast would enhance noninvasive MR tracking of cellular therapeutics. Therefore, an MRI methodology that selectively highlights areas of metallic objects has been developed. Inversion-recovery with ON-resonant water suppression (IRON) employs inversion of the magnetization in conjunction with a spectrally-selective on-resonant saturation prepulse. If imaging is performed after these prepulses, positive signal is obtained from off-resonant protons in close proximity to the metallic objects. The first successful use of IRON to produce positive contrast in areas of metallic spheres and SPIO-labeled stem cells in vitro and in vivo is presented.

Snapshot gradient-recalled echo-planar images of rat brains at long echo time at 9.4 T.

With improved B 0 homogeneity along with satisfactory gradient performance at high magnetic fields, snapshot gradient-recalled echo-planar imaging (GRE-EPI) would perform at long echo times (TEs) on the order of T2*, which intrinsically allows obtaining strongly T2*-weighted images with embedded substantial anatomical details in ultrashort time. The aim of this study was to investigate the feasibility and quality of long TE snapshot GRE-EPI images of rat brain at 9.4 T. When compensating for B 0 inhomogeneities, especially second-order shim terms, a 200 x 200 microm2 in-plane resolution image was reproducibly obtained at long TE (>25 ms). The resulting coronal images at 30 ms had diminished geometric distortions and, thus, embedded substantial anatomical details. Concurrently with the very consistent stability, such GRE-EPI images should permit to resolve functional data not only with high specificity but also with substantial anatomical details, therefore allowing coregistration of the acquired functional data on the same image data set.

Prevalence of left ventricular regional dysfunction in arrhythmogenic right ventricular dysplasia: a tagged MRI study.

BACKGROUND: Although arrhythmogenic right ventricular dysplasia (ARVD) predominantly affects the right ventricle (RV), genetic/molecular and histological changes are biventricular. Regional left ventricular (LV) function has not been systematically studied in ARVD. METHODS AND RESULTS: The study population included 21 patients with suspected ARVD who underwent evaluation with MRI including tagging. Eleven healthy volunteers served as control subjects. Peak systolic regional circumferential strain (Ecc, %) was calculated by harmonic phase from tagged MRI based on the 16-segment model. Patients who met ARVD Task Force criteria were classified as definite ARVD, whereas patients with a positive family history who had 1 additional minor criterion and patients without a family history with 1 major or 2 minor criteria were classified as probable ARVD. Of the 21 ARVD subjects, 11 had definite ARVD and 10 had probable ARVD. Compared with control subjects, probable ARVD patients had similar RV ejection fraction (58.9+/-6.2% versus 53.5+/-7.6%, P=0.20), but definite ARVD patients had significantly reduced RV ejection fraction (58.9+/-6.2% versus 45.2+/-6.0%, P=0.001). LV ejection fraction was similar in all 3 groups. Compared with control subjects, peak systolic Ecc was significantly less negative in 6 of 16 (37.5%) segments in definite ARVD and 3 of 16 segments (18.7%) in probable ARVD (all P<0.05). CONCLUSIONS: ARVD is associated with regional LV dysfunction, which appears to parallel degree of RV dysfunction. Further large studies are needed to validate this finding and to better define implications of subclinical segmental LV dysfunction.

Adaptive frequency tracking of the baseline ECG identifies the site of atrial fibrillation termination by catheter ablation

Multiple organization indices have been used to predict the outcome of stepwise catheter ablation in long-standing persistent atrial fibrillation (AF), however with limited success. Our study aims at developinginnovative organization indices from baseline ECG (i.e. during the procedure, before ablation) in orderto identify the site of AF termination by catheter ablation. Seventeen consecutive male patients (age60 ± 5 years, AF duration 7 ± 5 years) underwent a stepwise catheter ablation. Chest lead V6 was placedin the back (V6b). QRST cancelation was performed from chest leads V1 to V6b. Using an innovativeadaptive harmonic frequency tracking, two measures of AF organization were computed to quantify theharmonics components of ECG activity: (1) the adaptive phase difference variance (APD) between theAF harmonic components as a measure of AF regularity, and (2) and adaptive organization index (AOI)evaluating the cyclicity of the AF oscillations. Both adaptive indices were compared to indices computedusing a time-invariant approach: (1) ECG AF cycle length (AFCL), (2) the spectrum based organizationindex (OI), and (3) the time-invariant phase difference TIPD. Long-standing persistent AF was terminatedinto sinus rhythm or atrial tachycardia in 13/17 patients during stepwise ablation, 11 during left atriumablation (left terminated patients - LT), 2 during the right atrium ablation (right terminated patients -RT), and 4 were non terminated (NT) and required electrical cardioversion. Our findings showed that LTpatients were best separated from RT/NT before ablation by the duration of sustained AF and by AOI onchest lead V1 and APD from the dorsal lead V6b as compared to ECG AFCL, OI and TIPD, respectively. Ourresults suggest that adaptive measures of AF organization computed before ablation perform better thantime-invariant based indices for identifying patients whose AF will terminate during ablation within theleft atrium. These findings are indicative of a higher baseline organization in these patients that could beused to select candidates for the termination of AF by stepwise catheter ablation.© 2013 Elsevier Ltd. All rights reserved.

Metacognitive training for schizophrenia: a multicentre randomised controlled trial.

A psychotherapeutic approach for schizophrenia is now recommended as an adjuvant for psychopharmacology, since antipsychotic medications only have a partial impact especially as regards positive symptoms and insight. In addition, cognitive distortions and the lack of metacognitive skills might increase positive symptoms leading to poor social functioning. This underlines the need for specific approaches which target cognitive processes relevant for insight, and abilities in metacognition. Metacognitive training (MCT) is a structured group intervention, which enhances a patient's reflection on cognitive biases and improves problem-solving. The aim of our study was to assess MCTs' short term impact on insight, symptoms and quality of life. Fifty patients with schizophrenia or schizoaffective disorders and persistent positive symptoms (delusions or hallucinations) were enrolled in the study. After baseline assessment participants were randomised either to supportive therapy or MCT. Both groups used the same design (1h-session twice a week during 8weeks) although the basic knowledge given to participants was different between interventions. Participants were assessed at eight weeks based on the Scale to Assess Unawareness of Mental Disorder, Positive and Negative Syndrome Scale (PANSS), Psychotic Symptom Rating Scales, the Calgary Depression Scale for Schizophrenia and the Quality of Life Scale. Between-group differences were significant in favour of MCT on the PANSS positive scale. Between-group differences in post- and pre-test values showed a trend in favour of MCT for insight on hallucinations. Results of our study indicate that the MCT has an effect on reducing positive symptomatology, and a trend impact on insight and social functioning.

Eating and weight related cognitions in people with Schizophrenia: a case control study

ABSTRACT: BACKGROUND: Patients with antipsychotic-induced weight gain (WG) regularly report on unsuccessful dietary trials, which suggests strong biological weight gain drive that is extremely hard to overcome with thoughts, such that behaviour doesn't change despite some intent to change. The purpose of the present study was to assess cognitions specifically related to restrained eating in severely overweight patients with schizophrenia treated with antipsychotic drugs. METHODS: Forty outpatients with schizophrenia and 40 controls without psychiatric disability were included. Both groups were composed of one subgroup severely overweight (defined as a BMI > 28), and a comparison sample (BMI<28). The revised version of the Mizes Anorectic cognitive questionnaire (MAC-R) was used in this cross-sectional case-control study. RESULTS: Gender was significantly related to eating disorders cognition, women scoring higher than men. Patients with schizophrenia in general scored higher on the MAC-R total scale and on the MAC-R subscale 2, the latter score representing rigid weight regulation and fear of weight gain. When comparing the two groups of subjects with BMI < 28, it appeared that patients with schizophrenia also scored higher on MAC-R total scale, the subscales 2 and 3, the latter subscale 3, indicating altered self control and self-esteem. CONCLUSION: As is the case in weight gain of subjects without schizophrenia, the present results suggest that the cognitive distortions, as assessed by the MAC-R, may play an important role in weight gain also in patients with schizophrenia, and in weight gain associated with antipsychotic pharmacotherapy. Particular attention to these processes may help to improve the management of antipsychotic drugs induced weight gain

Homeostatic and circadian contribution to EEG and molecular state variables of sleep regulation.

STUDY OBJECTIVES: Besides their well-established role in circadian rhythms, our findings that the forebrain expression of the clock-genes Per2 and Dbp increases and decreases, respectively, in relation to time spent awake suggest they also play a role in the homeostatic aspect of sleep regulation. Here, we determined whether time of day modulates the effects of elevated sleep pressure on clock-gene expression. Time of day effects were assessed also for recognized electrophysiological (EEG delta power) and molecular (Homer1a) markers of sleep homeostasis. DESIGN: EEG and qPCR data were obtained for baseline and recovery from 6-h sleep deprivation starting at ZT0, -6, -12, or -18. SETTING: Mouse sleep laboratory. PARTICIPANTS: Male mice. INTERVENTIONS: Sleep deprivation. RESULTS: The sleep-deprivation induced changes in Per2 and Dbp expression importantly varied with time of day, such that Per2 could even decrease during sleep deprivations occurring at the decreasing phase in baseline. Dbp showed similar, albeit opposite dynamics. These unexpected results could be reliably predicted assuming that these transcripts behave according to a driven damped harmonic oscillator. As expected, the sleep-wake distribution accounted for a large degree of the changes in EEG delta power and Homer1a. Nevertheless, the sleep deprivation-induced increase in delta power varied also with time of day with higher than expected levels when recovery sleep started at dark onset. CONCLUSIONS: Per2 and delta power are widely used as exclusive state variables of the circadian and homeostatic process, respectively. Our findings demonstrate a considerable cross-talk between these two processes. As Per2 in the brain responds to both sleep loss and time of day, this molecule is well positioned to keep track of and to anticipate homeostatic sleep need. CITATION: Curie T; Mongrain V; Dorsaz S; Mang GM; Emmenegger Y; Franken P. Homeostatic and circadian contribution to EEG and molecular state variables of sleep regulation. SLEEP 2013;36(3):311-323.

Aggregation and errors in management accounting

Il est important pour les entreprises de compresser les informations détaillées dans des sets d'information plus compréhensibles. Au chapitre 1, je résume et structure la littérature sur le sujet « agrégation d'informations » en contrôle de gestion. Je récapitule l'analyse coûts-bénéfices que les comptables internes doivent considérer quand ils décident des niveaux optimaux d'agrégation d'informations. Au-delà de la perspective fondamentale du contenu d'information, les entreprises doivent aussi prendre en considération des perspectives cogni- tives et comportementales. Je développe ces aspects en faisant la part entre la comptabilité analytique, les budgets et plans, et la mesure de la performance. Au chapitre 2, je focalise sur un biais spécifique qui se crée lorsque les informations incertaines sont agrégées. Pour les budgets et plans, des entreprises doivent estimer les espérances des coûts et des durées des projets, car l'espérance est la seule mesure de tendance centrale qui est linéaire. A la différence de l'espérance, des mesures comme le mode ou la médiane ne peuvent pas être simplement additionnés. En considérant la forme spécifique de distributions des coûts et des durées, l'addition des modes ou des médianes résultera en une sous-estimation. Par le biais de deux expériences, je remarque que les participants tendent à estimer le mode au lieu de l'espérance résultant en une distorsion énorme de l'estimati¬on des coûts et des durées des projets. Je présente également une stratégie afin d'atténuer partiellement ce biais. Au chapitre 3, j'effectue une étude expérimentale pour comparer deux approches d'esti¬mation du temps qui sont utilisées en comptabilité analytique, spécifiquement « coûts basés sur les activités (ABC) traditionnelles » et « time driven ABC » (TD-ABC). Au contraire des affirmations soutenues par les défenseurs de l'approche TD-ABC, je constate que cette dernière n'est pas nécessairement appropriée pour les calculs de capacité. Par contre, je démontre que le TD-ABC est plus approprié pour les allocations de coûts que l'approche ABC traditionnelle. - It is essential for organizations to compress detailed sets of information into more comprehensi¬ve sets, thereby, establishing sharp data compression and good decision-making. In chapter 1, I review and structure the literature on information aggregation in management accounting research. I outline the cost-benefit trade-off that management accountants need to consider when they decide on the optimal levels of information aggregation. Beyond the fundamental information content perspective, organizations also have to account for cognitive and behavi¬oral perspectives. I elaborate on these aspects differentiating between research in cost accounti¬ng, budgeting and planning, and performance measurement. In chapter 2, I focus on a specific bias that arises when probabilistic information is aggregated. In budgeting and planning, for example, organizations need to estimate mean costs and durations of projects, as the mean is the only measure of central tendency that is linear. Different from the mean, measures such as the mode or median cannot simply be added up. Given the specific shape of cost and duration distributions, estimating mode or median values will result in underestimations of total project costs and durations. In two experiments, I find that participants tend to estimate mode values rather than mean values resulting in large distortions of estimates for total project costs and durations. I also provide a strategy that partly mitigates this bias. In the third chapter, I conduct an experimental study to compare two approaches to time estimation for cost accounting, i.e., traditional activity-based costing (ABC) and time-driven ABC (TD-ABC). Contrary to claims made by proponents of TD-ABC, I find that TD-ABC is not necessarily suitable for capacity computations. However, I also provide evidence that TD-ABC seems better suitable for cost allocations than traditional ABC.