The Social Value of Being Ambivalent: Self-Presentational Concerns in the Expression of Attitudinal Ambivalence

We tested whether individuals can exert control over the expression of attitudinal ambivalence and if this control is exerted with self-presentational concerns. Using the self-presentation paradigm, participants reported more ambivalence about Genetically Modified Organisms ("GMO") in a standard and a self-enhancement (present yourself positively) conditions than in a self-depreciation (present yourself negatively) condition, on both felt (Experiments 1a and 2a) and potential ambivalence, in its cognitive (Experiments 1b and 2b) and affective components (Experiments 1b and 2c). The role of ambivalent attitudes in conveying a positive social value was confirmed by the fact that the above effect was found on a controversial attitude object (GMOs) but the opposite appeared on a non-controversial one (e.g. tooth brushing, a truism; Experiment 3). Such a reversal was obtained by directly manipulating the perception of controversy on GMOs (Experiment 4). Attitudinal ambivalence may thus serve an adaptive function, i.e. achieving a positive social value.

Aortic vessel wall magnetic resonance imaging at 3.0 Tesla: a reproducibility study of respiratory navigator gated free-breathing 3D black blood magnetic resonance imaging.

The purpose of this study was to evaluate a free-breathing three-dimensional (3D) dual inversion-recovery (DIR) segmented k-space gradient-echo (turbo field echo [TFE]) imaging sequence at 3T for the quantification of aortic vessel wall dimensions. The effect of respiratory motion suppression on image quality was tested. Furthermore, the reproducibility of the aortic vessel wall measurements was investigated. Seven healthy subjects underwent 3D DIR TFE imaging of the aortic vessel wall with and without respiratory navigator. Subsequently, this sequence with respiratory navigator was performed twice in 10 healthy subjects to test its reproducibility. The signal-to-noise (SNR), contrast-to-noise ratio (CNR), vessel wall sharpness, and vessel wall volume (VWV) were assessed. Data were compared using the paired t-test, and the reproducibility of VWV measurements was evaluated using intraclass correlation coefficients (ICCs). SNR, CNR, and vessel wall sharpness were superior in scans performed with respiratory navigator compared to scans performed without. The ICCs concerning intraobserver, interobserver, and interscan reproducibility were excellent (0.99, 0.94, and 0.95, respectively). In conclusion, respiratory motion suppression substantially improves image quality of 3D DIR TFE imaging of the aortic vessel wall at 3T. Furthermore, this optimized technique with respiratory motion suppression enables assessment of aortic vessel wall dimensions with high reproducibility.

NS4B Self-Interaction through Conserved C-Terminal Elements Is Required for the Establishment of Functional Hepatitis C Virus Replication Complexes.

Hepatitis C virus (HCV) is an important human pathogen, persistently infecting more than 170 million individuals worldwide. Studies of the HCV life cycle have become possible with the development of cell culture systems supporting the replication of viral RNA and the production of infectious virus. However, the exact functions of individual proteins, especially of nonstructural protein 4B (NS4B), remain poorly understood. NS4B triggers the formation of specific, vesicular membrane rearrangements, referred to as membranous webs, which have been reported to represent sites of HCV RNA replication. However, the mechanism of vesicle induction is not known. In this study, a panel of 15 mutants carrying substitutions in the highly conserved NS4B C-terminal domain was generated. Five mutations had only a minor effect on replication, but two of them enhanced assembly and release of infectious virus. Ten mutants were replication defective and used for selection of pseudoreversions. Most of the pseudoreversions also localized to the highly conserved NS4B C-terminal domain and were found to restore replication competence upon insertion into the corresponding primary mutant. Importantly, pseudoreversions restoring replication competence also restored heterotypic NS4B self-interaction, which was disrupted by the primary mutation. Finally, electron microscopy analyses of membrane alterations induced by NS4B mutants revealed striking morphological abnormalities, which were restored to wild-type morphology by the corresponding pseudoreversion. These findings demonstrate the important role of the C-terminal domain in NS4B self-interaction and the formation of functional HCV replication complexes.

Transfer insensitive labeling technique (TILT): application to multislice functional perfusion imaging.

Cerebral blood flow can be studied in a multislice mode with a recently proposed perfusion sequence using inversion of water spins as an endogenous tracer without magnetization transfer artifacts. The magnetization transfer insensitive labeling technique (TILT) has been used for mapping blood flow changes at a microvascular level under motor activation in a multislice mode. In TILT, perfusion mapping is achieved by subtraction of a perfusion-sensitized image from a control image. Perfusion weighting is accomplished by proximal blood labeling using two 90 degrees radiofrequency excitation pulses. For control preparation the labeling pulses are modified such that they have no net effect on blood water magnetization. The percentage of blood flow change, as well as its spatial extent, has been studied in single and multislice modes with varying delays between labeling and imaging. The average perfusion signal change due to activation was 36.9 +/- 9.1% in the single-slice experiments and 38.1 +/- 7.9% in the multislice experiments. The volume of activated brain areas amounted to 1.51 +/- 0.95 cm3 in the contralateral primary motor (M1) area, 0.90 +/- 0.72 cc in the ipsilateral M1 area, 1.27 +/- 0.39 cm3 in the contralateral and 1.42 +/- 0.75 cm3 in the ipsilateral premotor areas, and 0.71 +/- 0.19 cm3 in the supplementary motor area.

Projecting the self to past and future in mental time

Introduction: Human experience takes place in the line of mental-time (MT) created through imagination of oneself in different time-points in past or future (self-projection in time). Here we manipulated self-projection in MT not only with respect to one's life-events but also with respect to one's faces from different past and future time-points. Methods: We here compared MTT with respect to one's facial images from different time points in past and future (study 1: MT-faces) as well as with respect to different past and future life events (study 2: MT-events). Participants were asked to make judgments about past and future face images and past and future events from three different time-points: the present (Now), eight years earlier (Past) or eight years later (Future). In addition, as a control task participants were asked to make recognition judgments with respect to faces and memory-related judgments with respect to events without changing their habitual self-location in time. Behavioral measures and functional magnetic resonance imaging (fMRI) activity after subtraction of recognition and memory related activities show both absolute MT and relative MT effects for faces and events, signifying a fundamental brain mechanism of MT, disentangled from episodic memory functions. Results: Behavioural and event-related fMRI activity showed three independent effects characterized by (1) similarity between past recollection and future imagination, (2) facilitation of judgments related to the future as compared to the past, and (3) facilitation of judgments related to time-points distant from the present. These effects were found with respect to faces and events suggesting that the brain mechanisms of MT are independent of whether actual life episodes have to be re-/pre-experienced and recruited a common cerebral network including the medial-temporal, precuneus, inferior-frontal, temporo-parietal, and insular cortices. Conclusions: These behavioural and neural data suggest that self-projection in time is a crucial aspect of MT, relying on neural structures encoding memory, mental imagery, and self. Furthermore our results emphasize the idea that mental temporal processing is more strongly directed to future prediction than to past recollection.

Self-selection and risk selection on the Swiss health insurance market

Abstract This thesis presents three empirical studies in the field of health insurance in Switzerland. First we investigate the link between health insurance coverage and health care expenditures. We use claims data for over 60 000 adult individuals covered by a major Swiss Health Insurance Fund, followed for four years; the data show a strong positive correlation between coverage and expenditures. Two methods are developed and estimated in order to separate selection effects (due to individual choice of coverage) and incentive effects ("ex post moral hazard"). The first method uses the comparison between inpatient and outpatient expenditures to identify both effects and we conclude that both selection and incentive effects are significantly present in our data. The second method is based on a structural model of joint demand of health care and health insurance and makes the most of the change in the marginal cost of health care to identify selection and incentive effects. We conclude that the correlation between insurance coverage and health care expenditures may be decomposed into the two effects: 75% may be attributed to selection, and 25 % to incentive effects. Moreover, we estimate that a decrease in the coinsurance rate from 100% to 10% increases the marginal demand for health care by about 90% and from 100% to 0% by about 150%. Secondly, having shown that selection and incentive effects exist in the Swiss health insurance market, we present the consequence of this result in the context of risk adjustment. We show that if individuals choose their insurance coverage in function of their health status (selection effect), the optimal compensations should be function of the se- lection and incentive effects. Therefore, a risk adjustment mechanism which ignores these effects, as it is the case presently in Switzerland, will miss his main goal to eliminate incentives for sickness funds to select risks. Using a simplified model, we show that the optimal compensations have to take into account the distribution of risks through the insurance plans in case of self-selection in order to avoid incentives to select risks.Then, we apply our propositions to Swiss data and propose a simple econometric procedure to control for self-selection in the estimation of the risk adjustment formula in order to compute the optimal compensations.

Effect of manganese chloride on the neurochemical profile of the rat hypothalamus.

Manganese (Mn(2+))-enhanced magnetic resonance imaging studies of the neuronal pathways of the hypothalamus showed that information about the regulation of food intake and energy balance circulate through specific hypothalamic nuclei. The dehydration-induced anorexia (DIA) model demonstrated to be appropriate for studying the hypothalamus with Mn(2+)-enhanced magnetic resonance imaging. Manganese is involved in the normal functioning of a variety of physiological processes and is associated with enzymes contributing to neurotransmitter synthesis and metabolism. It also induces psychiatric and motor disturbances. The molecular mechanisms by which Mn(2+) produces alterations of the hypothalamic physiological processes are not well understood. (1)H-magnetic resonance spectroscopy measurements of the rodent hypothalamus are challenging due to the distant location of the hypothalamus resulting in limited measurement sensitivity. The present study proposed to investigate the effects of Mn(2+) on the neurochemical profile of the hypothalamus in normal, DIA, and overnight fasted female rats at 14.1 T. Results provide evidence that γ-aminobutyric acid has an essential role in the maintenance of energy homeostasis in the hypothalamus but is not condition specific. On the contrary, glutamine, glutamate, and taurine appear to respond more accurately to Mn(2+) exposure. An increase in glutamine levels could also be a characteristic response of the hypothalamus to DIA.

Synaptic plasticity and the Warburg effect.

Functional brain imaging studies show that in certain brain regions glucose utilization exceeds oxygen consumption, indicating the predominance of aerobic glycolysis. In this issue, Goyal et al. (2014) report that this metabolic profile is associated with an enrichment in the expression of genes involved in synaptic plasticity and remodeling processes.

Self-measurement of blood pressure in clinical trials and therapeutic applications

Self-measurement of blood pressure (SMBP) is increasingly used to assess blood pressure outside the medical setting. A prerequisite for the wide use of SMBP is the availability of validated devices providing reliable readings when they are handled by patients. This is the case today with a number of fully automated oscillometric apparatuses. A major advantage of SMBP is the great number of readings, which is linked with high reproducibility. Given these advantages, one of the major indications for SMBP is the need for evaluation of antihypertensive treatment, either for individual patients in everyday practice or in clinical trials intended to characterize the effects of blood-pressure-lowering medications. In fact, SMBP is particularly helpful for evaluating resistant hypertension and detecting white-coat effect in patients exhibiting high office blood pressure under antihypertensive therapy. SMBP might also motivate the patient and improve his or her adherence to long-term treatment. Moreover, SMBP can be used as a sensitive technique for evaluating the effect of antihypertensive drugs in clinical trials; it increases the power of comparative trials, allowing one to study fewer patients or to detect smaller differences in blood pressure than would be possible with the office measurement. Therefore, SMBP can be regarded as a valuable technique for the follow-up of treated patients as well as for the assessment of antihypertensive drugs in clinical trials.

Thrombin-sensitive dual fluorescence imaging and therapeutic agent for detection and treatment of synovial inflammation in murine rheumatoid arthritis.

We have developed a thrombin-sensitive polymeric photosensitizer prodrug (T-PS) to selectively image and eradicate inflammatory lesions in rheumatoid arthritis (RA). Thrombin is a serine protease up-regulated in synovial tissues of rheumatoid arthritis (RA) patients. T-PS consists of a polymeric backbone, to which multiple photosensitizer (PS) units are tethered via short thrombin-cleavable peptide linkers. Fluorescence emission and phototoxicity of the prodrug are efficiently quenched due to the interaction of neighboring photosensitizer units. The prodrug is passively delivered to the inflammation site via the enhanced permeability and retention (EPR) effect. Subsequent site-selective proteolytic cleavage of the peptide linkers restores its photoactivity by increasing the mutual distance between PS. Whole animal imaging in murine collagen-induced arthritis, an experimental model of RA revealed a dose-dependent fluorescence increase in arthritic paws after systemic prodrug injection. In addition, administration of T-PS resulted in much higher fluorescence selectivity for arthritic joints as compared to the free PS. Irradiation of the arthritic joints induced light dose dependent phototoxic effects such as apoptosis, vascular damage and local hemorrhage. Long-term observations showed complete regression of the latter. Irradiated non-arthritic tissues or non-irradiated arthritic tissues showed no histological effects after photodynamic therapy with T-PS. This illustrates that T-PS can localize inflammatory lesions with excellent selectivity and induce apoptosis and vascular shut down after irradiation.

Metabolic predictors of obesity. Contribution of resting energy expenditure, thermic effect of food, and fuel utilization to four-year weight gain of post-obese and never-obese women.

This prospective study was designed to identify abnormalities of energy expenditure and fuel utilization which distinguish post-obese women from never-obese controls. 24 moderately obese, postmenopausal, nondiabetic women with a familial predisposition to obesity underwent assessments of body composition, fasting and postprandial energy expenditure, and fuel utilization in the obese state and after weight loss (mean 12.9 kg) to a post-obese, normal-weight state. The post-obese women were compared with 24 never-obese women of comparable age and body composition. Four years later, without intervention, body weight was reassessed in both groups. Results indicated that all parameters measured in the post-obese women were similar to the never-obese controls: mean resting energy expenditure, thermic effect of food, and fasting and postprandial substrate oxidation and insulin-glucose patterns. Four years later, post-obese women regained a mean of 10.9 kg while control subjects remained lean (mean gain 1.7 kg) (P < 0.001 between groups). Neither energy expenditure nor fuel oxidation correlated with 4-yr weight changes, whereas self-reported physical inactivity was associated with greater weight regain. The data suggest that weight gain in obesity-prone women may be due to maladaptive responses to the environment, such as physical inactivity or excess energy intake, rather than to reduced energy requirements.

Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers.

Background: Cocoa is rich in flavonoids, has anti-oxidative properties and increases the bioavailability of nitric oxide (NO). Adequate renal tissue oxygenation is crucial for the maintenance of renal function. The goal of this study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC). Methods: Ten healthy volunteers with preserved kidney function (mean age ± SD 35 ± 12 years, 70% women, BMI 21 ± 3 kg/m2) underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at least 1 week later, before and 2 hours after the intake of 1 g/kg WC. Results: The mean medullary R2* was lower after DC intake compared to baseline (28.2 ± 1.3 s-1 vs. 29.6 ± 1.3 s-1, p = 0.04), whereas cortical and medullary R2* values did not change after WC intake. The change in medullary R2* correlated with the level of circulating (epi)catechines, metabolites of flavonoids (r = 0.74, p = 0.037), and was independent of plasma renin activity. Conclusion: This study suggests for the first time an increase of renal medullary oxygenation after intake of dark chocolate. Whether this is linked to flavonoid-induced changes in renal perfusion or oxygen consumption, and whether cocoa has potentially renoprotective properties, merits further study.

Cell viability and noninvasive in vivo MRI tracking of 3D cell encapsulating self-assembled microcontainers.

Several molecular therapies require the implantation of cells that secrete biotherapeutic molecules and imaging the location and microenvironment of the cellular implant to ascertain its function. We demonstrate noninvasive in vivo magnetic resonance imaging (MRI) of self-assembled microcontainers that are capable of cell encapsulation. Negative contrast was obtained to discern the microcontainer with MRI; positive contrast was obtained in the complete absence of background signal. MRI on a clinical scanner highlights the translational nature of this research. The microcontainers were loaded with cells that were dispersed in an extracellular matrix, and implanted both subcutaneously and in human tumor xenografts in SCID mice. MRI was performed on the implants, and microcontainers retrieved postimplantation showed cell viability both within and proximal to the implant. The microcontainers are characterized by their small size, three dimensionality, controlled porosity, ease of parallel fabrication, chemical and mechanical stability, and noninvasive traceability in vivo.

Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial.

BACKGROUND: Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy. METHODS: Patients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com, number ISRCTN 25337470. FINDINGS: 1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2·76, 95% CI 1·17-6·51; p=0·021; HR for non-disabling stroke 3·00, 1·10-8·36; p=0·031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1·18, 0·40-3·55; p=0·76; HR for disabling or fatal stroke 1·41, 0·38-5·26; p=0·607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2·98, 1·29-6·93; p=0·011; HR for non-disabling stroke 6·34, 1·45-27·71; p=0·014), but there was no risk difference in patients with an ARWMC score of less than 7. INTERPRETATION: The presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, the European Union Research Framework Programme 5.