Existential values transformation in all organ transplantation: A qualitative prospective study.

Organ transplantation offers a treatment of choice for patients suffering from end stage illnesses. The aim of this IRB approved prospective qualitative study was to analyze patients’ psychological concerns from their inclusion on the waiting list for first organ transplantation (TX) (T1; N=71; kidney, K=30; liver, Li=11; lung, Lu=15; heart, H=15) and six months after TX (T2; N=49; K=15; Li=10; Lu=14; H=10). Semi-structured interviews were conducted at home or in a place selected by patients. Qualitative pattern analysis (QUAPA) of the verbatim transcriptions was applied. T1 (K) Patients maintained an apparent normality (87%), building emotional protection (23%), and developing a fatalist attitude towards life (43%). (Li) Physical limits were set to spare energy until TX (73%). Illness led to reevaluation of life values (66%). (Lu) Physical and psychological self-protection was prioritized when health declined (67%). Modified life values, fatalism (33%) and spirituality (27 %) were mentioned. (H) Patients husbanded physical (80%) and psychological (67%) resources and self-protection. Modified life values and fatalist attitude towards life were reported (40%). T2 (K) New perspective on life was described, with increase of empathy towards others (20%). (Li) Positive identity and life values modifications (60%), greater openness towards others, closeness to significant ones (30%) and a more self-centered attitude (30%) prioritizing the essential (20%) were reported. Lack of respect of life values generated anger (40%). (Lu) Setting existential priorities and increase in spirituality (64%), along with the development of new life values, greater openness to others (57%) and closeness to significant ones (21%) were underlined. Lack of respect of human values induced negative feelings (36%). Self-centered attitudes, setting limits to other people were mentioned (29%). (H) Change in life values with setting life priorities was reported (70%) with increase in spirituality, and the lack of respect of life values generated anger (50%). Self-centered attitudes were reported (60%). TX not only comes with positive physical benefits, but also with positive existential values and psychological transformation, and the development of a more altruistic attitude and humanistic values.

Callings in career: A typological approach to essential and optional components

A sense of calling in career is supposed to have positive implications for individuals and organizations but current theoretical development is plagued with incongruent conceptualizations of what does or does not constitute a calling. The present study used cluster analysis to identify essential and optional components of a presence of calling among 407 German undergraduate students from different majors. Three types of calling merged: "negative career self-centered", "pro-social religious", and "positive varied work orientation". All types could be described as vocational identity achieved (high commitment/high self-exploration), high in career confidence and career engagement. Not defining characteristics were centrality of work or religion, endorsement of specific work values, or positivity of core self-evaluations. The results suggest that callings entail intense self-exploration and might be beneficial because they correspond with identity achievement and promote career confidence and engagement while not necessarily having pro-social orientations. Suggestions for future research, theory and practice are suggested.

Fine structural variations of alphabetaTCRs selected by vaccination with natural versus altered self-antigen in melanoma patients.

Immunotherapy of cancer is often performed with altered "analog" peptide Ags optimized for HLA class I binding, resulting in enhanced immunogenicity, but the induced T cell responses require further evaluation. Recently, we demonstrated fine specificity differences and enhanced recognition of naturally presented Ag by T cells after vaccination with natural Melan-A/MART-1 peptide, as compared with analog peptide. In this study, we compared the TCR primary structures of 1489 HLA-A*0201/Melan-A(26-35)-specific CD8 T cells derived from both cohorts of patients. Although a strong preference for TRAV12-2 segment usage was present in nearly all patients, usage of particular TRAJ gene segments and CDR3alpha composition differed slightly after vaccination with natural vs analog peptide. Moreover, TCR beta-chain repertoires were broader after natural than analog peptide vaccination. In all patients, we observed a marked conservation of the CDR3beta amino acid composition with recurrent sequences centered on a glycyl-leucyl/valyl/alanyl-glycyl motif. In contrast to viral-specific TCR repertoires, such "public" motifs were primarily expressed by nondominant T cell clonotypes, which contrasted with "private" CDR3beta signatures frequently found in T cell clonotypes that dominated repertoires of individual patients. Interestingly, no differences in functional avidity were observed between public and private T cell clonotypes. Collectively, our data indicate that T cell repertoires generated against natural or analog Melan-A peptide exhibited slightly distinct but otherwise overlapping and structurally conserved TCR features, suggesting that the differences in binding affinity/avidity of TCRs toward pMHC observed in the two cohorts of patients are caused by subtle structural TCR variations.

Dormant and self-renewing hematopoietic stem cells and their niches.

In the mouse, over the last 20 years, a set of cell-surface markers and activities have been identified, enabling the isolation of bone marrow (BM) populations highly enriched in hematopoietic stem cells (HSCs). These HSCs have the ability to generate multiple lineages and are capable of long-term self-renewal activity such that they are able to reconstitute and maintain a functional hematopoietic system after transplantation into lethally irradiated recipients. Using single-cell reconstitution assays, various marker combinations can be used to achieve a functional HSC purity of almost 50%. Here we have used the differential expression of six of these markers (Sca1, c-Kit, CD135, CD48, CD150, and CD34) on lineage-depleted BM to refine cell hierarchies within the HSC population. At the top of the hierarchy, we propose a dormant HSC population (Lin(-)Sca1(+)c-Kit(+) CD48(-)CD150(+)CD34(-)) that gives rise to an active self-renewing CD34(+) HSC population. HSC dormancy, as well as the balance between self-renewal and differentiation activity, is at least, in part, controlled by the stem cell niches individual HSCs are attached to. Here we review the current knowledge about HSC niches and propose that dormant HSCs are located in niches at the endosteum, whereas activated HSCs are in close contact to sinusoids of the BM microvasculature.

Temporo-Parietal Junction encodes the Embodied Self: Neuro-Robotics, fMRI, and Lesion mapping.

Introduction: Neuroimaging of the self focused on high-level mechanisms such as language, memory or imagery of the self. Recent evidence suggests that low-level mechanisms of multisensory and sensorimotor integration may play a fundamental role in encoding self-location and the first-person perspective (Blanke and Metzinger, 2009). Neurological patients with out-of body experiences (OBE) suffer from abnormal self-location and the first-person perspective due to a damage in the temporo-parietal junction (Blanke et al., 2004). Although self-location and the first-person perspective can be studied experimentally (Lenggenhager et al., 2009), the neural underpinnings of self-location have yet to be investigated. To investigate the brain network involved in self-location and first-person perspective we used visuo-tactile multisensory conflict, magnetic resonance (MR)-compatible robotics, and fMRI in study 1, and lesion analysis in a sample of 9 patients with OBE due to focal brain damage in study 2. Methods: Twenty-two participants saw a video showing either a person's back or an empty room being stroked (visual stimuli) while the MR-compatible robotic device stroked their back (tactile stimulation). Direction and speed of the seen stroking could either correspond (synchronous) or not (asynchronous) to those of the seen stroking. Each run comprised the four conditions according to a 2x2 factorial design with Object (Body, No-Body) and Synchrony (Synchronous, Asynchronous) as main factors. Self-location was estimated using the mental ball dropping (MBD; Lenggenhager et al., 2009). After the fMRI session participants completed a 6-item adapted from the original questionnaire created by Botvinick and Cohen (1998) and based on questions and data obtained by Lenggenhager et al. (2007, 2009). They were also asked to complete a questionnaire to disclose the perspective they adopted during the illusion. Response times (RTs) for the MBD and fMRI data were analyzed with a 3-way mixed model ANOVA with the in-between factor Perspective (up, down) and the two with-in factors Object (body, no-body) and Stroking (synchronous, asynchronous). Quantitative lesion analysis was performed using MRIcron (Rorden et al., 2007). We compared the distributions of brain lesions confirmed by multimodality imaging (Knowlton, 2004) in patients with OBE with those showing complex visual hallucinations involving people or faces, but without any disturbance of self-location and first person perspective. Nine patients with OBE were investigated. The control group comprised 8 patients. Structural imaging data were available for normalization and co-registration in all the patients. Normalization of each patient's lesion into the common MNI (Montreal Neurological Institute) reference space permitted simple, voxel-wise, algebraic comparisons to be made. Results: Even if in the scanner all participants were lying on their back and were facing upwards, analysis of perspective showed that half of the participants had the impression to be looking down at the virtual human body below them, despite any cues about their body position (Down-group). The other participants had the impression to be looking up at the virtual body above them (Up-group). Analysis of Q3 ("How strong was the feeling that the body you saw was you?") indicated stronger self-identification with the virtual body during the synchronous stroking. RTs in the MBD task confirmed these subjective data (significant 3-way interaction between perspective, object and stroking). fMRI results showed eight cortical regions where the BOLD signal was significantly different during at least one of the conditions resulting from the combination of Object and Stroking, relative to baseline: right and left temporo-parietal junction, right EBA, left middle occipito-temporal gyrus, left postcentral gyrus, right medial parietal lobe, bilateral medial occipital lobe (Fig 1). The activation patterns in right and left temporo-parietal junction and right EBA reflected changes in self-location and perspective as revealed by statistical analysis that was performed on the percentage of BOLD change with respect to the baseline. Statistical lesion overlap comparison (using nonparametric voxel based lesion symptom mapping) with respect to the control group revealed the right temporo-parietal junction, centered at the angular gyrus (Talairach coordinates x = 54, y =-52, z = 26; p>0.05, FDR corrected). Conclusions: The present questionnaire and behavioural results show that - despite the noisy and constraining MR environment) our participants had predictable changes in self-location, self-identification, and first-person perspective when robotic tactile stroking was applied synchronously with the robotic visual stroking. fMRI data in healthy participants and lesion data in patients with abnormal self-location and first-person perspective jointly revealed that the temporo-parietal cortex especially in the right hemisphere encodes these conscious experiences. We argue that temporo-parietal activity reflects the experience of the conscious "I" as embodied and localized within bodily space.

Differing trends in the association between obesity and self-reported health in Portugal and Switzerland: data from national health surveys 1992-2007.

BACKGROUND: The escalating prevalence of obesity might prompt obese subjects to consider themselves as normal, as this condition is gradually becoming as frequent as normal weight. In this study, we aimed to assess the trends in the associations between obesity and self-rated health in two countries. METHODS: Data from the Portuguese (years 1995-6, 1998-6 and 2005-6) and Swiss (1992-3, 1997, 2002 and 2007) National Health Surveys were used, corresponding to more than 130,000 adults (64,793 for Portugal and 65,829 for Switzerland). Body mass index and self-rated health were derived from self-reported data. RESULTS: Obesity levels were higher in Portugal (17.5% in 2005-6 vs. 8.9% in 2007 in Switzerland, p < 0.001) and increased in both countries. The prevalence of participants rating their health as "bad" or "very bad" was higher in Portugal than in Switzerland (21.8% in 2005-6 vs 3.9% in 2007, p < 0.001). In both countries, obese participants rated more frequently their health as "bad" or "very bad" than participants with regular weight. In Switzerland, the prevalence of "bad" or "very bad" rates among obese participants, increased from 6.5% in 1992-3 to 9.8% in 2007, while in Portugal it decreased from 41.3% to 32.3%. After multivariate adjustment, the odds ratio (OR) of stating one self's health as "bad" or "very bad" among obese relative to normal weight participants, almost doubled in Switzerland: from 1.38 (95% confidence interval, CI: 1.01-1.87) in 1992-3 to 2.64 (95% CI: 2.14-3.26) in 2007, and similar findings were obtained after sample weighting. Conversely, no such trend was found in Portugal: 1.35 (95% CI: 1.23-1.48) in 1995-6 and 1.52 (95% CI: 1.37-1.70) in 2005-6. CONCLUSION: Obesity is increasing in Switzerland and Portugal. Obesity is increasingly associated with poorer self-health ratings in Switzerland but not in Portugal.

Fine structural variations of alphabeta TCRs selected by vaccination with natural versus altered self-antigen in melanoma patients

Immunotherapy of cancer is often performed with altered "analog" peptide Ags optimized for HLA class I binding, resulting in enhanced immunogenicity, but the induced T cell responses require further evaluation. Recently, we demonstrated fine specificity differences and enhanced recognition of naturally presented Ag by T cells after vaccination with natural Melan-A/MART-1 peptide, as compared with analog peptide. In this study, we compared the TCR primary structures of 1489 HLA-A*0201/Melan-A26-35-specific CD8 T cells derived from both cohorts of patients. Although a strong preference for TRAV12-2 segment usage was present in nearly all patients, usage of particular TRAJ gene segments and CDR3 composition differed slightly after vaccination with natural vs analog peptide. Moreover, TCR β-chain repertoires were broader after natural than analog peptide vaccination. In all patients, we observed a marked conservation of the CDR3β amino acid composition with recurrent sequences centered on a glycyl-leucyl/valyl/alanyl-glycyl motif. In contrast to viral-specific TCR repertoires, such "public" motifs were primarily expressed by nondominant T cell clonotypes, which contrasted with "private" CDR3β signatures frequently found in T cell clonotypes that dominated repertoires of individual patients. Interestingly, no differences in functional avidity were observed between public and private T cell clonotypes. Collectively, our data indicate that T cell repertoires generated against natural or analog Melan-A peptide exhibited slightly distinct but otherwise overlapping and structurally conserved TCR features, suggesting that the differences in binding affinity/avidity of TCRs toward pMHC observed in the two cohorts of patients are caused by subtle structural TCR variations.

Is the relationship between major depressive disorder and self-reported alcohol use disorder an artificial one ?

AIMS: Many studies have suggested a close relationship between alcohol use disorder (AUD) and major depressive disorder (MDD). This study aimed to test whether the relationship between self-reported AUD and MDD was artificially strengthened by the diagnosis of MDD. This association was tested comparing relationships between alcohol use and AUD for depressive people and non-depressive people. METHODS: As part of the Cohort Study on Substance Use Risk Factors, 4352 male Swiss alcohol users in their early twenties answered questions concerning their alcohol use, AUD and MDD at two time points. Generalized linear models for cross-sectional and longitudinal associations were calculated. RESULTS: For cross-sectional associations, depressive participants reported a higher number of AUD symptoms (β = 0.743, P < 0.001) than non-depressive participants. Moreover, there was an interaction (β = -0.204, P = 0.001): the relationship between alcohol use and AUD was weaker for depressive participants rather than non-depressive participants. For longitudinal associations, there were almost no significant relationships between MDD at baseline and AUD at follow-up, but the interaction was still significant (β = -0.249, P < 0.001). CONCLUSION: MDD thus appeared to be a confounding variable in the relationship between alcohol use and AUD, and self-reported measures of AUD seemed to be overestimated by depressive people. This result brings into question the accuracy of self-reported measures of substance use disorders. Furthermore, it adds to the emerging debate about the usefulness of substance use disorder as a concept, when heavy substance use itself appears to be a sensitive and reliable indicator.

Patients' Needs for Care in Public Mental Health: Unity and Diversity of Self-Assessed Needs for Care.

PURPOSE: Needs assessment is recognized to be a key element of mental health care. Patients tend to present heterogeneous profiles of needs. However, there is no consensus in previous research about how patients' needs are organized. This study investigates both general and specific dimensions of patients' needs for care. METHODS: Patients' needs were assessed with ELADEB, an 18-domain self-report scale. The use of a self-assessment scale represents a unique way of obtaining patients' perceptions. A patient-centered psychiatric practice facilitates empowerment as it is based on the patients' personal motivations, needs, and wants. Four seventy-one patients' profiles were analyzed through exploratory factor analysis. RESULTS: A four-factor bifactor model, including one general factor and three specific factors of needs, was most adequate. Specific factors were (a) "finances" and "administrative tasks"; (b) "transports," "public places," "self-care," "housework," and "food"; and (c) "family," "children," "intimate relationships," and "friendship." CONCLUSION: As revealed by the general factor, patients expressing urgent needs in some domains are also more susceptible to report urgent needs in several other domains. This general factor relates to high versus low utilizers of public mental healthcare. Patients also present specific needs in life domains, which are organized in three dimensions: management, functional disabilities, and familial and interpersonal relationships. These dimensions relate to the different types of existing social support described in the literature.

Extracorporeal membrane oxygenation support after heart explantation: a proposal on how to deal with hyperacute rejection of heart transplant

Purpose: In extreme situations, such as hyperacute rejection of heart transplant or major bleeding per-operating complications, an urgent heart explantation might be the only means of survival. The aim of this experimental study was to improve the surgical technique and the hemodynamics of an Extracorporeal Membrane Oxygenation (ECMO) support through a peripheral vascular access in an acardia model. Methods: An ECMO support was established in 7 bovine experiments (59±6.1 kg) by the transjugular insertion to the caval axis of a self-expanded cannula, with return through a carotid artery. After baseline measurements of pump flow and arterial and central venous pressure, ventricular fibrillation was induced (B), the great arteries were clamped, the heart was excised and right and left atria remnants, containing the pulmonary veins, were sutured together leaving an atrial septal defect (ASD) over the cannula in the caval axis. Measurements were taken with the pulmonary artery (PA) clamped (C) and anastomosed with the caval axis (D). Regular arterial and central venous blood gases tests were performed. The ANOVA test for repeated measures was used to test the null hypothesis and a Bonferroni t method for assessing the significance in the between groups pairwise comparison of mean pump flow. Results: Initial pump flow (A) was 4.3±0.6 L/min dropping to 2.8±0.7 L/min (P B-A= 0.003) 10 minutes after induction of ventricular fibrillation (B). After cardiectomy, with the pulmonary artery clamped (C) it augmented not significantly to 3.5±0.8 L/min (P C-B= 0.33, P C-A= 0.029). Finally, PA anastomosis to the caval axis was followed by an almost to baseline pump flow augmentation (4.1±0.7 L/min, P D-B= 0.009, P D-C= 0.006, P D-A= 0.597), permitting a full ECMO support in acardia by a peripheral vascular access. Conclusions: ECMO support in acardia is feasible, providing new opportunities in situations where heart must urgently be explanted, as in hyperacute rejection of heart transplant. Adequate drainage of pulmonary circulation is pivotal in order to avoid pulmonary congestion and loss of volume from the normal right to left shunt of bronchial vessels. Furthermore, the PA anastomosis to the caval axis not only improves pump flow but it also permits an ECMO support by a peripheral vascular access and the closure of the chest.

Melanoma patients respond to a cytotoxic T lymphocyte-defined self-peptide with diverse and nonoverlapping T-cell receptor repertoires.

HLA-A2+ melanoma patients develop naturally a strong CD8+ T cell response to a self-peptide derived from Melan-A. Here, we have used HLA-A2/peptide tetramers to isolate Melan-A-specific T cells from tumor-infiltrated lymph nodes of two HLA-A2+ melanoma patients and analyzed their TCR beta chain V segment and complementarity determining region 3 length and sequence. We found a broad diversity in Melan-A-specific immune T-cell receptor (TCR) repertoires in terms of both TCR beta chain variable gene segment usage and clonal composition. In addition, immune TCR repertoires selected in the patients were not overlapping. In contrast to previously characterized CD8+ T-cell responses to viral infections, this study provides evidence against usage of highly restricted TCR repertoire in the natural response to a self-differentiation tumor antigen.

Business research, self-fulfilling prophecy, and the inherent responsibility of scholars.

Business research and teaching institutions play an important role in shaping the way businesses perceive their relations to the broader society and its moral expectations. Hence, as ethical scandals recently arose in the business world, questions related to the civic responsibilities of business scholars and to the role business schools play in society have gained wider interest. In this article, I argue that these ethical shortcomings are at least partly resulting from the mainstream business model with its taken-for granted basic assumptions such as specialization or the value-neutrality of business research. Redefining the roles and civic responsibilities of business scholars for business practice implies therefore a thorough analysis of these assumptions if not their redefinition. The takenforgrantedness of the mainstream business model is questioned by the transformation of the societal context in which business activities are embedded. Its value-neutrality in turn is challenged by self-fulfilling prophecy effects, which highlight the normative influence of business schools. In order to critically discuss some basic assumptions of mainstream business theory, I propose to draw parallels with the corporate citizenship concept and the stakeholder theory. Their integrated approach of the relation between business practice and the broader society provides interesting insights for the social reembedding of business research and teaching.

Men and women differ in their cardiovascular responses to affective pictures

Empirical evidence supports the hypothesis that emotional states might contribute to cardiovascular disease and health through multiple pathways. To the extent that the acute cardiovascular response to emotional events plays a role in cardiovascular health and disease, an essential step in order to understand this possible link is to define the hemodynamic response to affective challenges. This was the aim of the present study. We assessed blood pressure (BP), heart rate (HR), stroke volume (SV), cardiac output, and total peripheral resistance (TPR) in response to 13 picture series in 18 men and 19 women (mean age 26) in order to investigate their hemodynamic responses associated with activation of the appetitive and defensive motivational systems underlying emotional experience. The hemodynamic parameters were recorded by finger-cuff photoplethysmography with Finometer™ (FMS Finapres Medical Systems, Amsterdam) and electrocardiography with the Lifeshirt system (VivoMetrics Inc., Ventura, California). Participants rated self-perceived pleasantness and arousal for each series. In men, BP and SV, but not TPR, increased with increasing self-rated arousal both for appetitive and defensive activation, whereas in women these relationships were almost absent, especially, for defensive activation. HR decelerated more in response to negative than positive and neutral pictures, and more so in men than women. These findings indicate striking sex differences. In particular, it is suggested that the sympathetic inotropic effect to the heart increases with increasing self-rated arousal strongly in men but only weakly in women. Regardless of sex differences, the modulation of the cardiovascular response to affective pictures along the dimensions of pleasantness and arousal is primarily myocardial, and the pattern of cardiovascular response is consistent with a configuration of cardiac sympathetic-parasympathetic coactivation. One possible implication of the observed sex differences concerns the link between affective states and cardiovascular health and disease. Men have a higher incidence of cardiovascular diseases than premenopausal women, and exaggerated sympathetic reactivity to emotional events is a potential pathophysiological mechanism. These findings extend current knowledge showing that under several acute behavioral challenges men demonstrate stronger cardiovascular reactivity than women.