More diversity, less tolerance? The effect of type of cultural diversity on the erosion of tolerance in Swiss municipalities

Immigration and the ways in which host societies receive newcomers pose challenges for modern civil societies. This article contributes to the ongoing discussion about how ethnic diversity influences tolerance towards immigrants. Compared to previous studies, we analyse tolerance as a sequential concept in order to uncover the effects of contextual diversity on attitudes towards immigrants and the granting of certain rights to this group. Moreover, we distinguish different shares of ethnic groups based on their ethnic and cultural origins both on the independent and dependent variable. The analysis relies on a subnational survey of sixty municipalities in Switzerland, revealing that only certain ethnic groups are seen as an economic and cultural threat.

Autonomy as a protective factor against the detrimental effects of ego depletion on tennis serve accuracy under pressure

It has been repeatedly demonstrated that athletes in a state of ego depletion do not perform up to their capabilities. We assume that autonomous self-control exertion, in contrast to forced self-control exertion, can serve as a buffer against ego depletion effects and can help individuals to show superior performance. In the present study, we applied a between-subjects design to test the assumption that autonomously exerted self-control is less detrimental for subsequent self-control performance in sports than is forced self-control exertion. In a primary self-control task, the level of autonomy was manipulated through specific instructions, resulting in three experimental conditions (autonomy-supportive: n = 19; neutral: n = 19; controlling: n = 19). As a secondary self-control task, participants executed a series of tennis serves under high-pressure conditions, and performance accuracy served as our dependent variable. As expected, a one-way between-groups ANOVA revealed that participants from the autonomy-supportive condition performed significantly better under pressure than did participants from the controlling condition. These results further highlight the importance of autonomy-supportive instructions in order to enable athletes to show superior achievements in high-pressure situations. Practical implications for the coach–athlete relationship are discussed.

Religious Diversity and Religious Vitality: New Measuring Strategies and Empirical Evidence

Quantitative studies of the conditions and consequences of religious diversity are based mostly on indices that measure the variety of religious membership in a particular region. However, this line of research has become stagnant, and the question of whether diversity affects religious vitality remains unanswered. This article attempts to shed new light on the discussion by measuring religious diversity differently and capturing religious vitality independently of membership figures. In particular, it contrasts the Herfindahl-Hirschman Index based on membership proportions with a second measure of diversity: an index of organizational diversity. Conversely, the dependent variable religious vitality is measured not by using rates of participation in religious organizations but via the Centrality of Religion Scale. Based on ecological and individual level data of forty-three local regions in Finland, Germany, and Slovenia and using multilevel analysis, our results suggest that religious diversity is related to religious vitality. However, the nature of this association differs across subgroups.

Situational adaptiveness of control orientation mediates relation between fixed-world view and youth well-being in three cultures

When proposing primary control (changing the world to fit self)/secondary control (changing self to fit the world) theory, Weisz et al. (1984) argued for the importance of the “serenity to accept the things I cannot change, the courage to change the things I can” (p. 967), and the wisdom to choose the right control strategy that fits the context. Although the dual processes of control theory generated hundreds of empirical studies, most of them focused on the dichotomy of PC and SC, with none of these tapped into the critical concept: individuals’ ability to know when to use what. This project addressed this issue by using scenario questions to study the impact of situationally adaptive control strategies on youth well-being. To understand the antecedents of youths’ preference for PC or SC, we also connected PCSC theory with Dweck’s implicit theory about the changeability of the world. We hypothesized that youths’ belief about the world’s changeability impacts how difficult it was for them to choose situationally adaptive control orientation, which then impacts their well-being. This study included adolescents and emerging adults between the ages of 18 and 28 years (Mean = 20.87 years) from the US (n = 98), China (n = 100), and Switzerland (n = 103). Participants answered a questionnaire including a measure of implicit theories about the fixedness of the external world, a scenario-based measure of control orientation, and several measures of well-being. Preliminary analyses of the scenario-based control orientation measures showed striking cross-cultural similarity of preferred control responses: while for three of the six scenarios primary control was the predominately chosen control response in all cultures, for the other three scenarios secondary control was the predominately chosen response. This suggested that youths across cultures are aware that some situations call for primary control, while others demand secondary control. We considered the control strategy winning the majority of the votes to be the strategy that is situationally adaptive. The results of a multi-group structural equation mediation model with the extent of belief in a fixed world as independent variable, the difficulties of carrying out the respective adaptive versus non-adaptive control responses as two mediating variables and the latent well-being variable as dependent variable showed a cross-culturally similar pattern of effects: a belief in a fixed world was significantly related to higher difficulties in carrying out the normative as well as the non-normative control response, but only the difficulty of carrying out the normative control response (be it primary control in situations where primary control is normative or secondary control in situations where secondary control is normative) was significantly related to a lower reported well-being (while the difficulty of carrying out the non-normative response was unrelated to well-being). While previous research focused on cross-cultural differences on the choice of PC or SC, this study shed light on the universal necessity of applying the right kind of control to fit the situation.

Limited redundancy in phosphorylation of retinoblastoma tumor suppressor protein by cyclin-dependent kinases in acute lymphoblastic leukemia

Cyclin-dependent kinases (CDKs) successively phosphorylate the retinoblastoma protein (RB) at the restriction point in G1 phase. Hyperphosphorylation results in functional inactivation of RB, activation of the E2F transcriptional program, and entry of cells into S phase. RB unphosphorylated at serine 608 has growth suppressive activity. Phosphorylation of serines 608/612 inhibits binding of E2F-1 to RB. In Nalm-6 acute lymphoblastic leukemia extracts, serine 608 is phosphorylated by CDK4/6 complexes but not by CDK2. We reasoned that phosphorylation of serines 608/612 by redundant CDKs could accelerate phospho group formation and determined which G1 CDK contributes to serine 612 phosphorylation. Here, we report that CDK4 complexes from Nalm-6 extracts phosphorylated in vitro the CDK2-preferred serine 612, which was inhibited by p16INK4a, and fascaplysin. In contrast, serine 780 and serine 795 were efficiently phosphorylated by CDK4 but not by CDK2. The data suggest that the redundancy in phosphorylation of RB by CDK2 and CDK4 in Nalm-6 extracts is limited. Serine 612 phosphorylation by CDK4 also occurred in extracts of childhood acute lymphoblastic leukemia cells but not in extracts of mobilized CD34+ hemopoietic progenitor cells. This phenomenon could contribute to the commitment of childhood acute lymphocytic leukemia cells to proliferate and explain their refractoriness to differentiation-inducing agents.

Age-dependent differences in demographics, risk factors, co-morbidity, etiology, management, and clinical outcome of acute ischemic stroke

BACKGROUND : Comparisons between younger and older stroke patients including comorbidities are limited. METHODS : Prospective data of consecutive patients with first ever acute ischemic stroke were compared between younger ( 45 years). RESULTS : Among 1004 patients, 137 (14 %) were regression analysis, there was no independent association between age and outcome (p = 0.206) or mortality (p = 0.073). Baseline NIHSS score (p < 0.0001), diabetes (p = 0.041), and CCI (p = 0.002) independently predicted an unfavorable outcome. CONCLUSIONS : Younger patients were more likely to be female, had different risk factors and etiologies and fewer co-morbidities. There was no independent association between age and clinical outcome or mortality.

Pericellular fibronectin is required for RhoA-dependent responses to cyclic strain in fibroblasts

To test the hypothesis that the pericellular fibronectin matrix is involved in mechanotransduction, we compared the response of normal and fibronectin-deficient mouse fibroblasts to cyclic substrate strain. Normal fibroblasts seeded on vitronectin in fibronectin-depleted medium deposited their own fibronectin matrix. In cultures exposed to cyclic strain, RhoA was activated, actin-stress fibers became more prominent, MAL/MKL1 shuttled to the nucleus, and mRNA encoding tenascin-C was induced. By contrast, these RhoA-dependent responses to cyclic strain were suppressed in fibronectin knockdown or knockout fibroblasts grown under identical conditions. On vitronectin substrate, fibronectin-deficient cells lacked fibrillar adhesions containing alpha5 integrin. However, when fibronectin-deficient fibroblasts were plated on exogenous fibronectin, their defects in adhesions and mechanotransduction were restored. Studies with fragments indicated that both the RGD-synergy site and the adjacent heparin-binding region of fibronectin were required for full activity in mechanotransduction, but not its ability to self-assemble. In contrast to RhoA-mediated responses, activation of Erk1/2 and PKB/Akt by cyclic strain was not affected in fibronectin-deficient cells. Our results indicate that pericellular fibronectin secreted by normal fibroblasts is a necessary component of the strain-sensing machinery. Supporting this hypothesis, induction of cellular tenascin-C by cyclic strain was suppressed by addition of exogenous tenascin-C, which interferes with fibronectin-mediated cell spreading.

Co2-dependent vasomotor reactivity of cerebral arteries in patients with severe traumatic brain injury: time course and effect of augmentation of cardiac output with dobutamine

Failing cerebral blood flow (CBF) autoregulation may contribute to cerebral damage after traumatic brain injury (TBI). The purpose of this study was to describe the time course of CO(2)-dependent vasoreactivity, measured as CBF velocity in response to hyperventilation (vasomotor reactivity [VMR] index). We included 13 patients who had had severe TBI, 8 of whom received norepinephrine (NE) based on clinical indication. In these patients, measurements were also performed after dobutamine administration, with a goal of increasing cardiac output by 30%. Blood flow velocity was measured with transcranial Doppler ultrasound in both hemispheres. All patients except one had an abnormal VMR index in at least one hemisphere within the first 24 h after TBI. In those patients who did not receive catecholamines, mean VMR index recovered within the first 48 to 72 h. In contrast, in patients who received NE within the first 48 h period, VMR index did not recover on the second day. Cardiac output and mean CBF velocity increased significantly during dobutamine administration, but VMR index did not change significantly. In conclusion, CO(2) vasomotor reactivity was abnormal in the first 24 h after TBI in most of the patients, but recovered within 48 h in those patients who did not receive NE, in contrast to those eventually receiving the drug. Addition of dobutamine to NE had variable but overall insignificant effects on CO(2) vasomotor reactivity.

Prognostic impact of lymph node ratio outperforms positive lymph nodes and lymph nodes harvested: a time-dependent analysis in mismatch repair-proficient and –deficient colrectal cancers

Objective: We compare the prognostic strength of the lymph node ratio (LNR), positive lymph nodes (+LNs) and collected lymph nodes (LNcoll) using a time-dependent analysis in colorectal cancer patients stratified by mismatch repair (MMR) status. Method: 580 stage III-IV patients were included. Multivariable Cox regression analysis and time-dependent receiver operating characteristic (tROC) curve analysis were performed. The Area under the Curve (AUC) over time was compared for the three features. Results were validated on a second cohort of 105 stage III-IV patients. Results: The AUC for the LNR was 0.71 and outperformed + LNs and LNcoll by 10–15 % in both MMR-proficient and deficient cancers. LNR and + LNs were both significant (p<0.0001) in multivariable analysis but the effect was considerably stronger for the LNR [LNR: HR=5.18 (95 % CI: 3.5–7.6); +LNs=1.06 (95 % CI: 1.04–1.08)]. Similar results were obtained for patients with >12 LNcoll. An optimal cut off score for LNR=0.231 was validated on the second cohort (p<0.001). Conclusion: The LNR outperforms the + LNs and LNcoll even in patients with >12 LNcoll. Its clinical value is not confounded by MMR status. A cut-of score of 0.231 may best stratify patients into prognostic subgroups and could be a basis for the future prospective analysis of the LNR.

Leydig-cell tumour in children: variable clinical presentation, diagnostic features, follow-up and genetic analysis of four cases

BACKGROUND: Testicular tumours are relatively uncommon in infants and children, accounting for only 1-2% of all paediatric solid tumours. Of these approximately 1.5% are Leydig-cell tumours. Further, activating mutations of the luteinizing hormone receptor gene (LHR), as well as of the G protein genes, such as Gsalpha (gsp) and Gialpha (gip2) subunits, and cyclin-dependent kinase gene 4(CDK4) have been associated with the development of several endocrine neoplasms. AIMS/METHODS: In this report, the clinical variability of Leydig-cell tumours in four children is described. The LHR-, gsp-, gip2- and CDK4 genes were investigated to establish the possible molecular pathogenesis of the variable phenotype of the Leydig-cell tumours. RESULTS: No activating mutations in these genes were found in the four Leydig-cell tumours studied. Therefore, the absence of activating mutations in LHR, as well as in both the 'hot spot' regions for activating mutations within the G-alpha subunits and in the regulatory 'hot spot' on the CDK4 genes in these tumours indicates molecular heterogeneity among Leydig-cell tumours. CONCLUSION: Four children with a variable phenotype caused by Leydig-cell tumours are described. A molecular analysis of all the 'activating' genes and mutational regions known so far was performed, but no abnormalities were found. The lessons learnt from these clinically variable cases are: perform ultrasound early and most importantly, consider discrepancies between testicular swelling, tumour size and androgen production.

Increased sensitivity in mapping task demand in visuospatial processing using reaction-time-dependent hemodynamic response predictors in rapid event-related fMRI

Searching for the neural correlates of visuospatial processing using functional magnetic resonance imaging (fMRI) is usually done in an event-related framework of cognitive subtraction, applying a paradigm comprising visuospatial cognitive components and a corresponding control task. Besides methodological caveats of the cognitive subtraction approach, the standard general linear model with fixed hemodynamic response predictors bears the risk of being underspecified. It does not take into account the variability of the blood oxygen level-dependent signal response due to variable task demand and performance on the level of each single trial. This underspecification may result in reduced sensitivity regarding the identification of task-related brain regions. In a rapid event-related fMRI study, we used an extended general linear model including single-trial reaction-time-dependent hemodynamic response predictors for the analysis of an angle discrimination task. In addition to the already known regions in superior and inferior parietal lobule, mapping the reaction-time-dependent hemodynamic response predictor revealed a more specific network including task demand-dependent regions not being detectable using the cognitive subtraction method, such as bilateral caudate nucleus and insula, right inferior frontal gyrus and left precentral gyrus.

Platelet activation induces metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen

Glycoprotein (GP) VI, the primary collagen receptor on platelets, has been shown to have variable expression, possibly as a consequence of immune modulation. The present study was designed to determine the mechanism by which GP VI clearance occurs. We found that direct activation of GP VI both by a GP VI-specific antibody and by GP VI ligands (collagen and convulxin) reduced binding of biotinylated convulxin to the stimulated platelets. Analysis of immunoblots of platelets and supernatants showed that the stimulated platelets contained less GP VI, while the soluble fraction contained a 57-kDa cleavage product. Stimulation of platelets with PAR-1 agonists (TRAP peptide and thrombin) also caused GP VI cleavage, although the amount of GP VI loss was less than that observed with direct GP VI ligands. The metalloproteinase (MMP) inhibitors GM6001 and TAPI prevented both the clearance of GP VI from the platelet surface and the appearance of the soluble cleavage product. Induction of GP VI cleavage caused specific down-regulation of collagen-induced platelet aggregation, providing a mechanism for the modulation of platelet responsiveness to this important platelet agonist.

Direct adipotropic actions of atorvastatin: differentiation state-dependent induction of apoptosis, modulation of endocrine function, and inhibition of glucose uptake

Statins exert anti-inflammatory, anti-atherogenic actions. The mechanisms responsible for these effects remain only partially elucidated. Diabetes and obesity are characterized by low-grade inflammation. Metabolic and endocrine adipocyte dysfunction is known to play a crucial role in the development of these disorders and the related cardiovascular complications. Thus, direct modulation of adipocyte function may represent a mechanism of pleiotropic statin actions. We investigated effects of atorvastatin on apoptosis, differentiation, endocrine, and metabolic functions in murine white and brown adipocyte lines. Direct exposure of differentiating preadipocytes to atorvastatin strongly reduced lipid accumulation and diminished protein expression of the differentiation marker CCAAT/enhancer binding protein-beta (CEBP-beta). In fully differentiated adipocytes, however, lipid accumulation remained unchanged after chronic atorvastatin treatment. Furthermore, cell viability was reduced in response to atorvastatin treatment in proliferating and differentiating preadipocytes, but not in differentiated cells. Moreover, atorvastatin induced apoptosis and inhibited protein kinase B (AKT) phosphorylation in proliferating and differentiating preadipocytes, but not in differentiated adipocytes. On the endocrine level, direct atorvastatin treatment of differentiated white adipocytes enhanced expression of the pro-inflammatory adipokine interleukin-6 (IL-6), and downregulated expression of the insulin-mimetic and anti-inflammatory adipokines visfatin and adiponectin. Finally, these direct adipotropic endocrine effects of atorvastatin were paralleled by the acute inhibition of insulin-induced glucose uptake in differentiated white adipocytes, while protein expression of the thermogenic uncoupling protein-1 (UCP-1) in brown adipocytes remained unchanged. Taken together, our data for the first time demonstrate direct differentiation state-dependent effects of atorvastatin including apoptosis, modulation of pro-inflammatory and glucostatic adipokine expression, and insulin resistance in adipose cells. These differential interactions may explain variable clinical observations.

Angiopoietin-2 deficiency decelerates age-dependent vascular changes in the mouse retina

Retinae of aged humans show signs of vascular regression. Vascular regression involves a mismatch between Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) expression. We used heterozygous Ang-2 deficient (Ang2LacZ) mice to evaluate murine retinal vascular changes and gene expression of growth factors. Vascular changes were assessed by quantitative retinal morphometry and gene expression levels of growth factors were measured by quantitative PCR. The numbers of endothelial cells and pericytes did not change in the Ang2LacZ retinae with age, whereas they decreased throughout the age spectrum studied in the wild type retinae. Moreover, vascular regression significantly decelerated in the heterozygous Ang2LacZ retinae (200% to 1 month), while the formation of acellular capillaries was significantly increased at 13 months in the wild type retinae (340% to 1 month). Gene expression analysis revealed that VEGF, Ang-1, PDGF-B and Ang2 mRNA levels were decreased in the wild type retinae at 9 month of age. However, the decrease of Ang-2 was smaller compared with other genes. While VEGF levels dropped in wild type mice up to 60% compared to 1 month, VEGF increased in heterozygous Ang-2 deficient retinae at an age of 9 months (141% to 1 month). Similarly, Ang-1 levels decreased in wild type mice (45% to 1 month), but remained stable in Ang2LacZ mice. These data suggest that Ang-2 gene dose reduction decelerates vasoregression in the retina with age. This effect links to higher levels of survival factors such as VEGF and Ang-1, suggesting that the ratio of these factors is critical for capillary cell survival.

Risk of adverse effects of intensified treatment in insulin-dependent diabetes mellitus: a meta-analysis

While the benefits of intensified insulin treatment in insulin-dependent (Type 1) diabetes mellitus (IDDM) are well recognized, the risks have not been comprehensively characterized. We examined the risk of severe hypoglycaemia, ketoacidosis, and death in a meta-analysis of randomized controlled trials. The MEDLINE database, reference lists, and specialist journals were searched electronically or by hand to identify relevant studies with at least 6 months of follow-up and the monitoring of glycaemia by glycosylated haemoglobin measurements. Logistic regression was used for calculation of combined odds ratios and 95% confidence intervals (95% CI). The influence of covariates was examined by including covariate-by-treatment interaction terms. Methodological study quality was assessed and sensitivity analyses were performed. Fourteen trials were identified. These contributed 16 comparisons with 1028 patients allocated to intensified and 1039 allocated to conventional treatment. A total of 846 patients suffered at least one episode of severe hypoglycaemia, 175 patients experienced ketoacidosis and 26 patients died. The combined odds ratio (95% CI) for hypoglycaemia was 2.99 (2.45-3.64), for ketoacidosis 1.74 (1.27-2.38) and for death from all causes 1.40 (0.65-3.01). The risk of severe hypoglycaemia was determined by the degree of normalization of glycaemia achieved (p=0.005 for interaction term), with the results from the Diabetes Control and Complications Trial (DCCT) in line with the other trials. Ketoacidosis risk depended on the type of intensified treatment used. Odds ratios (95% CI) were 7.20 (2.95-17.58) for exclusive use of pumps, 1.13 (0.15-8.35) for multiple daily injections and 1.28 (0.90-1.83) for trials offering a choice between the two (p = 0.004 for interaction). Mortality was significantly (p = 0.007) increased for causes potentially associated with acute complications (7 vs 0 deaths, 5 deaths attributed to ketoacidosis, and 2 sudden deaths), and non-significantly (p = 0.16) decreased for macrovascular causes (3 vs 8 deaths). We conclude that there is a substantial risk of severe adverse effects associated with intensified insulin treatment. Mortality from acute metabolic causes is increased; however, this is largely counterbalanced by a reduction in cardiovascular mortality. The excess of severe hypoglycemia in the DCCT is not exceptional. Multiple daily injection schemes may be safer than treatment with insulin pumps.