bluuebunny/crossref_metadata_2025 huggingface dataset:
Bortezomib Induces Nuclear Translocation of IκBα Resulting in Gene-Specific Suppression of NF-κB–Dependent Transcription and Induction of Apoptosis in CTCL
Authors: Juvekar Ashish , Manna Subrata , Ramaswami Sitharam , Chang Tzu-Pei , Vu Hai-Yen , Ghosh Chandra C. , Celiker Mahmut Y. , Vancurova Ivana
Published: January 2011

Cutaneous T-cell lymphoma (CTCL) is characterized by constitutive activation of nuclear factor κB (NF-κB), which plays a crucial role in the survival of CTCL cells and their resistance to apoptosis. NF-κB activity in CTCL is inhibited by the proteasome inhibitor bortezomib; however, the mechanisms remained unknown. In this study, we investigated mechanisms by which bortezomib suppresses NF-κB activity in CTCL Hut-78 cells. We demonstrate that bortezomib and MG132 suppress NF-κB activity in Hut-78 cells by a novel mechanism that consists of inducing nuclear translocation and accumulation of IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), which then associates with NF-κB p65 and p50 in the nucleus and inhibits NF-κB DNA binding activity. Surprisingly, however, while expression of NF-κB–dependent antiapoptotic genes cIAP1 and cIAP2 is inhibited by bortezomib, expression of Bcl-2 is not suppressed. Chromatin immunoprecipitation indicated that cIAP1 and cIAP2 promoters are occupied by NF-κB p65/50 heterodimers, whereas Bcl-2 promoter is occupied predominantly by p50/50 homodimers. Collectively, our data reveal a novel mechanism of bortezomib function in CTCL and suggest that the inhibition of NF-κB–dependent gene expression by bortezomib is gene specific and depends on the subunit composition of NF-κB dimers recruited to NF-κB–responsive promoters. Mol Cancer Res; 9(2); 183–94. ©2011 AACR.
Contrasting Monosymptomatic Patients with Hallucinations and Delusions in First-Episode Psychosis Patients: A Five-Year Longitudinal Follow-Up Study
Authors: Evensen Julie , Røssberg Jan Ivar , Haahr Ulrik , ten Velden Hegelstad Wenche , Joa Inge , Johannessen Jan Olav , Langeveld Hans , Larsen T.K. , Melle Ingrid , Opjordsmoen Stein , Rund Bjørn Rishovd , Simonsen Erik , Sundet Kjetil , Vaglum Per , Friis Svein , McGlashan Thomas
Published: January 2011

Background: The main aim of this study was to identify subgroups of patients characterized by having hallucinations only or delusions only and to examine whether these groups differed with regard to demographic characteristics, clinical characteristics and outcome factors, including suicidality. Methods: Out of 301 consecutively admitted patients with first-episode psychosis, individuals with delusions only (D) and hallucinations only (H) were identified based on Positive and Negative Syndrome Scale (PANSS) items P1 (delusions) and P3 (hallucinations) scores at baseline and through 4 follow-up interviews over 5 years. The subgroups were compared with regard to demographic data, premorbid functioning, duration of untreated psychosis, clinical variables, time to remission and suicidality. Results: Two groups of patients were identified; H (n = 16) and D (n = 106). 179 patients experienced both hallucinations and delusions (dual symptom group). The H group was significantly younger, had a longer duration of untreated psychosis, poorer premorbid function and better insight than the D group. Notably, the H group scored higher on measures of suicidality, and at 5 years follow-up a significantly higher proportion of patients was lost to suicide in this group. The dual symptom group was closer to the D group on significant parameters, including suicidality and suicide rate. Conclusions: Patients with hallucinations only can be separated from patients with delusions only and the subgroups differ with regard to demographical data, clinical variables and notably with regard to suicidality. These findings suggest distinctions in the underlying biological and psychological processes involved in hallucinations and in delusions.
Unexplained Somatic Symptoms during Major Depression: Prevalence and Clinical Impact in a National Sample of Italian Psychiatric Outpatients
Authors: Perugi Giulio , Canonico Pier Luigi , Carbonato Paolo , Mencacci Claudio , Muscettola Giovanni , Pani Luca , Torta Riccardo , Vampini Claudio , Fornaro Michele , Parazzini Fabio , Dumitriu Arina ,   on behalf of the Come To Me Study Group
Published: January 2011

Background: The aim of this study was to explore the prevalence and impact of unexplained somatic symptoms during major depression. Sampling and Methods: A total of 560 consecutive outpatients with a major depressive episode according to the DSM-IV (text revision) were evaluated in 30 psychiatric facilities throughout Italy. ‘Unexplained’ somatic symptoms were evaluated using the 30-item Somatic Symptoms Checklist (SSCL-30). Somatic symptoms were considered explained if they were best accounted for as coming from a concomitant physical illness or side effects. Patients evaluated their own mood symptomatology using the Zung questionnaires for depression and anxiety and the Hypomania Checklist-32. Results: According to the SSCL-30, only 90 subjects (16.1%) had no unexplained somatic symptoms, while 231 (41.3%) had 1–5 unexplained symptoms and 239 (42.7%) had more than 5. Asthenia was the most commonly observed unexplained somatic symptom (53% of patients). Unexplained somatic symptoms were more common in females and among those suffering from major depression and depression not otherwise specified rather than in patients with recurrent major depression and bipolar disorders. No relationship between unexplained somatic symptoms and hypomanic features was observed. Conclusions: The presence of a large number of unexplained somatic symptoms is associated with more severe depression and higher rates of misdiagnosis and inappropriate treatment.
Patterns of Inflammatory Responses in Large and Small Airways in Smokers with and without Chronic Obstructive Pulmonary Disease
Authors: Isajevs Sergejs , Taivans Immanuels , Svirina Darja , Strazda Gunta , Kopeika Uldis
Published: January 2011

Background: Chronic obstructive pulmonary disease (COPD) is characterised by progressive and irreversible airway obstruction. Smoking causes persistent inflammation in lung tissue. However, differences in inflammatory responses between the large and small airways have not been systematically explored among smokers with and without COPD. Objectives: The aim of our research was to characterise the expression and localisation of NF-ĸBp65 and histone deacetylase 2 (HDAC2) as well as inflammatory cell (macrophages, lymphocytes, neutrophils) distribution in large and small airways, in nonsmokers and in smokers with and without COPD. Methods: Nineteen nonsmokers, 20 smokers with normal lung ventilation function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate NF-ĸBp65 and HDAC2 expression and identify inflammatory cells in airways. Results: COPD patients had increased NF-ĸBp65 expression compared to nonsmokers and smokers without COPD, in both large and small airways, which corresponded to increased numbers of macrophages, CD8+ T lymphocytes and neutrophils. COPD patients had more macrophages in large compared to small airways and more CD8+ T lymphocytes and neutrophils in small compared to large airways. HDAC2 expression was significantly downregulated in smokers with COPD in small compared to large airways. Conclusions: Our findings indicate a nonuniform distribution of inflammatory cells throughout the bronchial tree. However, in both smokers with and without COPD, similar patterns of inflammatory processes occur in both large and small airways. The difference between smokers with and without COPD is only quantitative.
Challenges of Longevity in Developed Countries: Vascular Prevention of Dementia as an Immediate Clue to Tackle an Upcoming Medical, Social and Economic Stretch
Authors: Wehling Martin , Groth Hans
Published: January 2011

Aging of societies, with increasing life expectancies, results in surging health care expenditures, as older age is closely associated with an increasing number of chronic and often resource-consuming diseases. Among those, dementia has the greatest impact on an individual’s quality of life, the level of burden on the family and expenditures to finance nursing. Currently, pharmacological dementia treatment is exclusively focused on neurotransmitter-modulating medicines. Unfortunately, their effectiveness is not interminable, and the effect size limited. Novel approaches such as vaccinations are currently under vigorous investigation, but still far from translation into clinical practice. Thus, the consequent exploitation of opportunities which are already known is pivotal. Dementia prevention can become effective without delay if the vascular components of dementia are aggressively targeted through life style modifications as well as the treatment of vascular risk factors (e.g. hypertension). Longevity will become a significant burden for developed countries already within the next 10–20 years. By 2020, the 80+ generation will increase by at least 30% and in 2030 by at least 50%, compared to 2010. If the associated dementia challenge is not adequately tackled, longevity may no longer remain desirable for aged societies.
A Comparison of Different Definitions of Growth Response in Short Prepubertal Children Treated with Growth Hormone
Authors: Bang P. , Bjerknes R. , Dahlgren J. , Dunkel L. , Gustafsson J. , Juul A. , Kriström B. , Tapanainen P. , Åberg V.
Published: January 2011

Background: How to define poor growth response in the management of short growth hormone (GH)-treated children is controversial. Aim: Assess various criteria of poor response. Subjects and Methods: Short GH-treated prepubertal children [n = 456; height (Ht) SD score (SDS) ≤–2] with idiopathic GH deficiency (IGHD, n = 173), idiopathic short stature (ISS, n = 37), small for gestational age (SGA, n = 54), organic GHD (OGHD, n = 40), Turner syndrome (TS, n = 43), skeletal dysplasia (n = 15), other diseases (n = 46) or syndromes (n = 48) were evaluated in this retrospective multicenter study. Median age at GH start was 6.3 years and Ht SDS –3.2. Results: Median [25–75 percentile] first-year gain in Ht SDS was 0.65 (0.40–0.90) and height velocity (HtV) 8.67 (7.51–9.90) cm/year. Almost 50% of IGHD children fulfilled at least one criterion for poor responders. In 28% of IGHD children, Ht SDS gain was <0.5 and they had lower increases in median IGF-I SDS than those with Ht SDS >0.5. Only IGHD patients with peak stimulated growth hormone level <3 µg/l responded better than those with ISS. A higher proportion of children with TS, skeletal dysplasia or born SGA had Ht SDS gain <0.5. Conclusion: Many children respond poorly to GH therapy. Recommendations defining a criterion may help in managing short stature patients.
Local Skin Pharmacokinetics of Talarozole, a New Retinoic Acid Metabolism-Blocking Agent
Authors: Baert B. , De Spiegeleer B.
Published: January 2011

Talarozole is a new highly potent and selective azole derivative which inhibits cytochrome-P450-dependent all-trans-retinoic acid catabolism. It is in clinical development for the treatment of psoriasis and acne. However, no local pharmacokinetic data on the diffusion behaviour of talarozole in the skin itself are available. As topical application might be an interesting alternative to oral therapy because of the reduced systemic side effects, the aim of this study was to assess the transdermal behaviour of topically applied talarozole, including its within-skin distribution. Franz diffusion cell experiments with talarozole dissolved in different pharmaceutically relevant solvents (i.e. propylene glycol, oleolyl macrogol glyceride, isopropyl myristate, diethylene glycol monoethylether, ethanol, caprylic/capric triglyceride and caprylocaproyl macrogol glyceride) were performed to assess the transdermal behaviour of talarozole. Talarozole slightly diffused into the skin only when dissolved in propylene glycol, isopropyl myristate or ethanol. Although only 0.1% of the dose applied was found in the skin itself after 12–24 h, this was sufficient to achieve local concentrations well above the half-maximal inhibitory concentration value for talarozole. The distribution of talarozole within the skin was investigated: 80% was located in the epidermis, while the remaining 20% was found in the dermis. The epidermal concentration of talarozole achieved after a single topical application was sufficiently high to enable the potential induction of local retinoid-like effects.
Double Trouble from Sunburn: UVB-Induced Erythema Is Associated with a Transient Decrease in Skin Pigmentation
Authors: Casetti F. , Miese A. , Mueller M.L. , Simon J.C. , Schempp C.M.
Published: January 2011

Background: Ultraviolet B (UVB) radiation may cause an immediate inflammatory response followed by a delayed increase in skin pigmentation. The early time course of erythema and pigmentation has so far not been monitored simultaneously by photometric measurements. Methods: Test areas on the volar forearms of 15 volunteers were irradiated with 210 mJ/cm2 UVB. Skin erythema and pigmentation were determined photometrically at time 0, after 6 h, and after 1, 2, 3 and 7 days. Punch biopsies were taken before irradiation, after 6 h and after 7 days. Melanocytes were stained using the DOPA method. Results: UVB irradiation caused an increase in skin erythema at all time points, peaking at 24 h and slowly decreasing until day 7. Surprisingly, this was associated with a pronounced decrease in skin pigmentation at early readings. DOPA staining of melanocytes confirmed this observation. Only after 7 days was there an increase in skin pigmentation over the initial levels. Conclusions: Acute UVB-induced skin erythema seems to be associated with increased susceptibility to the deleterious effects of solar radiation due to a concomitant decrease in skin pigmentation. These findings underline the importance of avoiding even moderate sunburns and of slowly adapting the skin to solar radiation.
Haemostatic effects of a new combined oral contraceptive, nomegestrol acetate/17β-estradiol, compared with those of levonorgestrel/ethinyl estradiol
Authors: Alhenc-Gelas Martine , Thomas Jean-Louis , Bachelot-Loza Christilla , Remones Veronique , Dali Ali Fouad , Aiach Martine , Scarabin Pierre-Yves , Gaussem Pascale
Published: January 2011

Use of oral contraceptives (OC) that combine a progestogen with synthetic ethinyl estradiol (EE) is associated with increased risk of venous thromboembolism. NOMAC/E2 is a new monophasic OC that combines nomegestrol acetate (NOMAC), a highly selective progestogen, with 17β-estradiol (E2). The study objective was to compare the effects on markers of haemostasis of NOMAC/E2 (2.5 mg/1.5 mg) versus the second-generation OC, levonorgestrel (LNG)/EE (100 μg/20 μg). Healthy women (age 18–38 years) received once-daily treatment for three consecutive 28-day cycles in a double-blind, randomised study: either NOMAC/E2 for 24 days with a four-day placebo interval (n=45) or LNG/ EE for 21 days with a seven-day placebo interval (n=45) per cycle. Mean changes from baseline to end-of-treatment in coagulation markers, including prothrombin fragment 1+2 (primary endpoint), fibrinolysis markers and platelet functions were assessed. Mean prothrombin fragment 1+2 levels (primary endpoint) did not increase with NOMAC/E2 compared with LNG/EE ( –0.02 vs. +0.08 nM, p<0.01). Other significant differences between NOMAC/E2 and LNG/EE were mean changes in antithrombin (+0.3% vs. –4.4%, p<0.001), activated protein C resistance – normalised ratio (+0.20 vs. +0.46, p<0.01), D-dimer ( –53 vs. +43 ng/ml, p<0.001), plasminogen (+6% vs. +30%, p<0.0001) and plasminogen activator inhibitor-1 ( –3.1 vs. –8.0 ng/ml, p<0.001). There was no effect of either treatment on platelet aggregation. The NOMAC/E2 pill regimen has fewer adverse effects on blood biological coagulation and fibrinolysis markers than LNG/EE. This suggests that NOMAC/E2 could have a more favourable venous thromboembolism risk profile than LNG/EE; further epidemiological data are required to confirm this.
Simultaneous intravital imaging of macrophage and neutrophil behaviour during inflammation using a novel transgenic zebrafish
Authors: Gray Caroline , Loynes Catherine , Whyte Moira , Crossman David , Renshaw Stephen , Chico Timothy
Published: January 2011

The zebrafish is an outstanding model for intravital imaging of inflammation due to its optical clarity and the ability to express fluorescently labelled specific cell types by transgenesis. However, although several transgenic labelling myeloid cells exist, none allow distinction of macrophages from neutrophils. This prevents simultaneous imaging and examination of the individual contributions of these important leukocyte subtypes during inflammation. We therefore used Bacterial Artificial Chromosome (BAC) recombineering to generate a transgenic Tg(fms:GAL4.VP16)i186, in which expression of the hybrid transcription factor Gal4-VP16 is driven by the fms (CSF1R) promoter. This was then crossed to a second transgenic expressing a mCherry-nitroreductase fusion protein under the control of the Gal4 binding site (the UAS promoter), allowing intravital imaging of mCherry-labelled macrophages. Further crossing this compound transgenic with the neutrophil transgenic Tg(mpx:GFP)i114 allowed clear distinction between macrophages and neutrophils and simultaneous imaging of their recruitment and behaviour during inflammation. Compared with neutrophils, macrophages migrate significantly more slowly to an inflammatory stimulus. Neutrophil number at a site of tissue injury peaked around 6 hours post injury before resolving, while macrophage recruitment increased until at least 48 hours. We show that macrophages were effectively ablated by addition of the prodrug metronidazole, with no effect on neutrophil number. Crossing with Tg(Fli1:GFP)y1 transgenic fish enabled intravital imaging of macrophage interaction with endothelium for the first time, revealing that endothelial contact is associated with faster macrophage migration. Tg(fms:GAL4.VP16)i186 thus provides a powerful tool for intravital imaging and functional manipulation of macrophage behaviour during inflammation.
Association between the Pulmonary Embolism Severity Index (PESI) and short-term clinical deterioration
Authors: Hariharan Praveen , Takayesu James Kimo , Kabrhel Christopher
Published: January 2011

The Pulmonary Embolism Severity Index (PESI) has been shown to predict 30 and 90 day mortality after PE. However, whether the PESI predicts patients who will be free of clinically adverse outcomes during a typical hospitalisation is not known. Retrospective analysis of Emergency Department patients with PE from May 2006 to April 2008. We compiled demographics, data to calculate the PESI and a composite outcome. Patients were considered to have a negative PESI if they were in category I or II (≤85 points). Patients were considered to have the composite outcome if, within five days of diagnosis, they: A) had recurrent PE; B) developed a new cardiac dysrhythmia; C) required advanced cardiac life support; D) required respiratory support; E) required vasopressors; F) received thrombolysis; G) had major bleeding; H) returned to the ED; I) died. We enrolled 245 patients with PE. Of these, 115 (47%) were male, 204 (83%) were white. The mean age was 57 ± 17 years. The PESI identified 109 (44%) as low risk and 136 (56%) as high risk. Sixty-one (26%) patients had the outcome, of whom nine (14%) were char-acterised as low risk by the PESI. Test characteristics were: sensitivity 86% (95% confidence interval [CI]: 75%-93%), specificity 55% (95% CI: 47%-62%), NPV 63% (95% CI: 55%-70%), PPV 40% (95% CI: 31%-49%), LR(+) 1.9 (95% CI: 1.57–2.30) and LR(-) 0.26 (95% CI: 0.14–0.48). Of the patients categorised by the PESI as safe for discharge, 14% had an adverse clinical event or required a hospital-based intervention within the first five days after PE diagnosis. Improvements in the risk stratification of patients with PE are still needed.

* Presented at the American College of Emergency Physicians, Scientific Assembly, Boston, 2009.
Molecular imaging of macrophage protease activity in cardiovascular inflammation in vivo
Authors: Quillard Thibaut , Croce Kevin , Jaffer Farouc , Weissleder Ralph , Libby Peter
Published: January 2011

Macrophages contribute pivotally to cardiovascular diseases (CVD), notably to atherosclerosis. Imaging of macrophages in vivo could furnish new tools to advance evaluation of disease and therapies. Proteolytic enzymes serve as key effectors of many macrophage contributions to CVD. Therefore, intravital imaging of protease activity could aid evaluation of the progress and outcome of atherosclerosis, aortic aneurysm formation, or rejection of cardiac allografts. Among the large families of proteases, matrix metalloproteinases (MMPs) and cysteinyl cathepsins have garnered the most interest because of their participation in extra-cellular matrix remodelling. These considerations have spurred the development of dedicated imaging agents for protease activity detection. Activatable fluorescent probes, radiolabelled inhibitors, and nanoparticles are currently under exploration for this purpose. While some agents and technologies may soon see clinical use, others will require further refinement. Imaging of macrophages and protease activity should provide an important adjunct to understanding pathophysiology in vivo, evaluating the effects of interventions, and ultimately aiding clinical care.
Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II)
Authors: Dahl Ola , Huo Michael , Kurth Andreas , Hantel Stefan , Hermansson Karin , Schnee Janet , Friedman Richard , Eriksson Bengt ,   for the RE-NOVATE II Study Group
Published: January 2011

This trial compared the efficacy and safety of oral dabigatran, a direct thrombin inhibitor, versus subcutaneous enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty. A total of 2,055 patients were randomised to 28–35 days treatment with oral dabigatran, 220 mg once-daily, starting with a half-dose 1–4 hours after surgery, or subcutaneous enoxaparin 40 mg once-daily, starting the evening before surgery. The primary efficacy outcome was a composite of total venous thromboembolism [VTE] (venographic or symptomatic) and death from all-causes. The main secondary composite outcome was major VTE (proximal deep-vein thrombosis or non-fatal pulmonary embolism) plus VTE-related death. The main safety outcome was major bleeding. In total, 2,013 were treated, of whom 1,577 operated patients were included in the primary efficacy analysis. The primary efficacy outcome occurred in 7.7% of the dabigatran group versus 8.8% of the enoxaparin group, risk difference (RD) –1.1% (95%CI –3.8 to 1.6%); p<0.0001 for the pre-specified non-inferiority margin. Major VTE plus VTE-related death occurred in 2.2% of the dabigatran group versus 4.2% of the enoxaparin group, RD –1.9% (-3.6% to –0.2%); p=0.03. Major bleeding occurred in 1.4% of the dabigatran group and 0.9% of the enoxaparin group (p=0.40). The incidence of adverse events, including liver enzyme elevations and cardiac events, during treatment was similar between the groups. Extended prophylaxis with oral dabigatran 220 mg once-daily was as effective as sub-cutaneous enoxaparin 40 mg once-daily in reducing the risk of VTE after total hip arthroplasty, and superior to enoxaparin for reducing the risk of major VTE. The risk of bleeding and safety profiles were similar.
Venous and arterial thrombosis – pathogenesis and the rationale for anticoagulation
Authors: Esmon Charles , Turpie Alexander
Published: January 2011

Thromboembolic disorders are major causes of morbidity and mortality. It is well-recognised that the pathogenesis is different for arterial and venous thrombosis; however, both involve coagulation activation. Anticoagulants are used for the prevention and treatment of a wide variety of thromboembolic and related conditions. Agents with anti-inflammatory properties in addition to anticoagulation may be particularly beneficial. Traditional anticoagulants, although effective, are associated with certain limitations. Understanding the pathological processes associated with thrombosis and the rational target for anticoagulation is essential, not only for the development of safer and more effective agents, but also for better clinical management of patients who require anticoagulation therapy. In recent years, new oral agents that target single enzymes of the coagulation cascade have been developed – some of those are in advanced stages of clinical development. Based on scientific rationale, both factor Xa and thrombin are viable targets for effective anticoagulation.
Cross-Cultural Variations in Naïve Psychology among 2-year-olds: A Comparison of Children in the United Kingdom and Singapore
Authors: Lim Ai Keow , Williams Joanne M. , Cebula Katie R. , Annaz Dagmara
Published: January 2011

Children’s understanding of naïve psychology is the main focus of this study. Research evidence suggests that 2- and 3-year-olds understand some aspects of naïve psychology. By 4 years, they develop internal representations of mental states. Previous studies have also reported cross-cultural variations in naïve psychology development. The majority of this research has focused on Western individualistic societies such as Australia, Europe and North America, and Eastern collectivism societies such as China and Japan. Singapore with its blend of Eastern and Western values represents a unique case for comparison with Western societies. This paper reports a cross-cultural study of young children’s developing understanding of naïve psychology in Edinburgh, UK and Singapore. It addresses three main questions: (a) Are there cross-cultural differences in the development of naïve psychology?; (b) What are children’s performance sequences on naïve psychology tasks?; and (c) Are naïve psychology concepts coherent? The participants were 87 children from the UK (n=43, mean age 2 years 4 months) and Singapore (n=44, mean age 2 years 5 months). This study incorporated several established tasks of pretence, desires, emotions, perceptions, appearance-reality and false-beliefs to investigate children’s understanding of non-representational and representational mental states. The results showed no gross cross-cultural differences. However, significant cultural differences in performance on two tasks and differences in the coherence of naïve psychology concepts were identified. The results highlight the importance of considering subtle cultural influences on children’s developing understanding of various aspects of naïve psychology.
Intuitive Moral Judgments are Robust across Variation in Gender, Education, Politics and Religion: A Large-Scale Web-Based Study
Authors: Banerjee Konika , Huebner Bryce , Hauser Marc
Published: January 2011

Research on moral psychology has frequently appealed to three, apparently consistent patterns: (1) Males are more likely to engage in transgressions involving harm than females; (2) educated people are likely to be more thorough in their moral deliberations because they have better resources for rationally navigating and evaluating complex information; (3) political affiliations and religious ideologies are an important source of our moral principles. Here, we provide a test of how four factors ‐ gender, education, politics and religion ‐ affect intuitive moral judgments in unfamiliar situations. Using a large-scale sample of participants (n=8778) who voluntarily logged on to the internet-based Moral Sense Test (available online at http://moral.wjh.harvard.edu), we analyzed responses to 145 unique moral and conventional scenarios that varied widely in content. Although each demographic or cultural factor sometimes yielded a statistically significant difference in the predicted direction (e.g., men giving more utilitarian judgments than women; religious individuals giving more deontological/rule-based judgments than atheists), these differences were consistently associated with extremely small effect sizes. We conclude that gender, education, politics and religion are likely to be relatively insignificant for moral judgments of unfamiliar scenarios. We discuss these results in light of current debates concerning the mechanisms underlying our moral judgments and, especially, the idea that we share a universal moral sense that constrains the range of cross-cultural variation.
The Role of Culture in Affective Empathy: Cultural and Bicultural Differences
Authors: Cassels Tracy G. , Chan Sherilynn , Chung Winnie
Published: January 2011

Empathy is essential for healthy relationships and overall well-being. Affective empathy is the emotional response to others’ distress and can take two forms: personal distress or empathic concern. In Western cultures, high empathic concern and low personal distress have been implicated in increased prosocial behaviour (e.g., Eisenberg et al., 1989) and better emotion management and peer relations (e.g., Eisenberg and Fabes, 1998). Various factors have been examined with respect to affective empathy, but the role of culture has received little attention. Previous work suggests that children from East Asian cultures compared to those from Western cultures experience greater personal distress and less empathic concern (e.g., Trommsdorff, 1995), but no work has specifically examined these differences in adolescents or individuals who identify as ‘bicultural’. The current research examines cultural differences in affective empathy using the Interpersonal Reactivity Index (Davis, 1980) in an adolescent and young adult sample (n=190) and examines how empathy relates to social-emotional health in bicultural individuals. Consistent with research on children, East Asian adolescents reported greater personal distress and less empathic concern than their Western counterparts. The bicultural individuals’ scores fell in between the East Asian and Western groups, but revealed significant differences from their ‘uni-cultural’ peers, demonstrating shared influences of community and family. Importantly, however, the relationship between affective empathy and social-emotional health in bicultural individuals was the same as for Western individuals. The current results provide an important first step in understanding the different cultural influences on empathic responding in a previously understudied population ‐ bicultural individuals.
Classifying ‘Eoliths’: How Cultural Cognition Featured in Arguments Surrounding Claims for the Earliest Human Artefacts as these Developed Between 1880 and 1900
Authors: Ellen Roy , Muthana Angela
Published: January 2011

‘Eoliths’ were crude but purportedly humanly worked stones that exercised a great deal of scientific interest between about 1870 and 1930. They became a problem in the context of the debate surrounding the existence of pre-humans in Europe before the beginning of the Pleistocene epoch, and are now mostly reckoned to be of non-human origin. This paper addresses the way in which a network of geologists and prehistorians associated with Benjamin Harrison, the celebrated collector of the first English eoliths, attempted to make sense of barely recognizable artefacts in the period immediately following the establishment of human antiquity in the face of orthodox creationist chronologies. Harrison and his associates did so by innovating a series of criteria, names, categories and crosscutting classifications drawn from their own cultural experience, and typologies available to them through the comparative ethnography of technology. Using concepts and insights developed in cognitive anthropology, we shall attempt to shed light on a controversy in the history of science that has implications for our understanding of the way in which scientists more generally employ ‘provisional classifications’, folk categories and vernacular terminology in order to make sense of domains of intractable data at the frontiers of knowledge.
The Zeus Problem: Why Representational Content Biases Cannot Explain Faith in Gods
Authors: Gervais Will M. , Henrich Joseph
Published: January 2011

In a recent article, Barrett (2008) argued that a collection of five representational content features can explain both why people believe in God and why people do not believe in Santa Claus or Mickey Mouse. In this model ‐ and within the cognitive science of religion as a whole ‐ it is argued that representational content biases are central to belief. In the present paper, we challenge the notion that representational content biases can explain the epidemiology of belief. Instead, we propose that representational content biases might explain why some concepts become widespread, but that context biases in cultural transmission are necessary to explain why people come to believe in some counterintuitive agents rather than others. Many supernatural agents, including those worshipped by other cultural groups, meet Barrett’s criteria. Nevertheless, people do not come to believe in the gods of their neighbors. This raises a new challenge for the cognitive science of religion: the Zeus Problem. Zeus contains all of the features of successful gods, and was once a target for widespread belief, worship, and commitment. But Zeus is no longer a target for widespread belief and commitment, despite having the requisite content to fulfill Barrett’s criteria. We analyze Santa Claus, God, and Zeus with both content and context biases, finding that context ‐ not content ‐ explains belief. We argue that a successful cognitive science of religious belief needs to move beyond simplistic notions of cultural evolution that only include representational content biases.
Implicit Voodoo: Electrodermal Activity Reveals a Susceptibility to Sympathetic Magic
Authors: Hood Bruce M. , Donnelly Katherine , Leonards Ute , Bloom Paul
Published: January 2011

Although young children might be uncertain about the nature of certain representations, most modern adults would explicitly maintain that photographs have no ongoing physical connection the objects that they depict. We demonstrate here in three studies that destruction of a photograph of a sentimental object produces significantly more electrodermal activity than destruction of photographs of other control objects. This response is not attributable to anxiety about being observed whilst destroying the picture, nor is it entirely due to simple visual association ‐ the same response occurs when the photograph does not resemble the object. We suggest that this effect may reflect a tacit acceptance of “sympathetic magic”.
Who Framed Sarah Palin? Viewer Reactions to the 2008 Vice Presidential Debate
Authors: McKinney Mitchell S. , Rill Leslie A. , Watson Rebekah G.
Published: January 2011

This study analyzes viewer assessments of Sara Palin’s vice presidential debate performance. Specifically, a national sample of debate viewers evaluated Palin and her vice presidential opponent Joe Biden on both image and issue measures before and after viewing their debate performance. We argue that the attendant media attention surrounding Palin before her debate performance—mostly negative in tone—framed Palin as unfit for office and created expectations that she would fail in her debate with Joe Biden. On several measures, however, Palin’s debate performance actually exceeded the low-bar of expectations that had been set, thus benefiting her in terms of viewers’ assessments of her debate performance.
Premarketing Surveillance of Ibuprofen Suppositories in Febrile Children
Authors: Hadas Dan , Youngster Ilan , Cohen Avner , Leibovitch Eugene , Shavit Itai , Erez Ilan , Uziel Yosef , Berkovitch Matitiahu
Published: January 2011

In many countries, ibuprofen is available only in oral formulations. The authors aimed to investigate parental satisfaction and possible adverse reactions among children receiving newly marketed ibuprofen suppositories, prior to their arrival at the pharmaceutical points of distribution. Children needing antipyretic medication were recruited from 11 pediatric wards and clinics in Israel. Each patient received ibuprofen suppositories (5-10 mg/kg/dose) after completing a data collection form. After 3 to 7 days of treatment, information regarding parent satisfaction, possible adverse reactions, and concomitant use of drugs was obtained. Overall, 490 children completed the study. Parents’ satisfaction was high (4.5 ± 0.47 on a scale of 1-5), and 92.2% reported that they would use the medication in the future. Adverse reactions were reported in 8 patients (1.63%, 95% confidence interval = 1.77-3.25), the most common being diarrhea. Rectal administration of ibuprofen suppositories is well tolerated and overall satisfaction and the repeated expected use were high.
A coupled mixed-mode delamination model for laminated composites
Authors: Bui V.Q. , Iannucci L. , Robinson P. , Pinho S.T.
Published: January 2011

Cohesive elements have now become commonplace in many commercial finite element codes. Their use in impact and crash and other complex composite design problems requires the development of more advanced cohesive element formulations capable of predicting mixed-mode behavior during a complex loading. A cohesive zone model is developed for the simulation of delaminations in laminated composites under mixed-mode loadings, based on a coupling between the normal and tangential components of the relative displacement across an interlaminar interface. Featuring a unique characterization of degraded states, this coupling enables a simultaneous loss of loading capacity of the interface in normal and tangential directions, once the criteria on delamination growth are satisfied. Moreover, the variation of mode participation during the delamination process is effectively considered. A comparison between numerical simulations and experimental data on typical delamination tests shows the robustness and the potential of the model.
Effects of ultraviolet radiation and condensation on static and dynamic compression behavior of neat and nanoclay infused epoxy/glass composites
Authors: Zainuddin S. , Hosur M.V. , Barua R. , Kumar Ashok , Jeelani S.
Published: January 2011

Effects of ultraviolet radiation and condensation on the static and dynamic compressive properties of composites with and without nanoclay were investigated. Specimens were exposed to ultraviolet radiation (UV), and alternate ultraviolet radiation and condensation (UC) conditions for 5, 10, and 15 days, respectively. Compression test results showed an increase in strength and modulus with increase in strain rate and nanoclay weight percent loading. However, properties degraded upon conditioning with nanoclay infused systems showing less degradation. Scanning electron micrographs of fractured samples show better interfacial bonding in nanoclay infused composites in 2 wt. % system showing best properties.
Performance of Dental Ceramics: Challenges for Improvements
Authors: Rekow E.D. , Silva N.R.F.A. , Coelho P.G. , Zhang Y. , Guess P. , Thompson V.P.
Published: January 2011

The clinical success of modern dental ceramics depends on an array of factors, ranging from initial physical properties of the material itself, to the fabrication and clinical procedures that inevitably damage these brittle materials, and the oral environment. Understanding the influence of these factors on clinical performance has engaged the dental, ceramics, and engineering communities alike. The objective of this review is to first summarize clinical, experimental, and analytic results reported in the recent literature. Additionally, it seeks to address how this new information adds insight into predictive test procedures and reveals challenges for future improvements.
Sensory Transduction in Human Teeth with Inflamed Pulps
Authors: Ajcharanukul O. , Chidchuangchai W. , Charoenlarp P. , Vongsavan N. , Matthews B.
Published: January 2011

The effects of pulpal inflammation on the sensitivity of dentin to cold (5°C) and negative hydrostatic pressure (−300 mm Hg) stimuli in man were compared, since recent evidence suggests that these stimuli excite different classes of sensory receptors. Dentin was exposed in premolars in 14 participants aged 15-25 years. Stimuli were applied to etched dentin immediately after cavity preparation and after the cavity had been filled with gutta percha for 7 days. This treatment increased significantly the intensity of pain produced by cold, and at the same time decreased that evoked by negative pressure stimuli. Pulpal blood flow was increased in the treated teeth, indicating that their pulps were inflamed. It is concluded that the sensory receptors responsible for the response to cold were probably sensitive to some change other than an outward flow of fluid in dentinal tubules, which would be caused by both forms of stimulus.
Effectiveness of Search Strategies for Qualitative Research About Barriers and Facilitators of Program Delivery
Authors: Pearson Mark , Moxham Tiffany , Ashton Kate
Published: January 2011

Electronic database search strategies have developed substantially over the course of the past two decades, but their optimal use within a broader search strategy remains unclear. This article evaluates the use of a range of search strategies to identify qualitative evidence on the implementation of cardiovascular disease (CVD) prevention programs. Within the time-limited context of the production of a policy-relevant systematic review, the authors found the protocol-driven, targeted, and reference-checking search strategies to be the most effective, while obtaining authors’ suggestions proved to be a resource-intensive process with negligible results. Weaknesses in the indexing of qualitative research in electronic literature databases mean that the sensitivity of searches may need to be reduced to allow time for other search strategies to be implemented. Expert knowledge may be optimally used through involving experts in the design and implementation of a search strategy, rather than solely as a source of citations.
“It’s a Feel. That’s What a Lot of Our Evidence Would Consist of ”: Public Health Practitioners’ Perspectives on Evidence
Authors: Higgins Joan Wharf , Strange Karen , Scarr Jennifer , Pennock Michael , Barr Victoria , Yew Ann , Drummond Janine , Terpstra Jennifer
Published: January 2011

This article describes how evidence is defined and used in two British Columbia public health departments during the implementation of a Healthy Living initiative in 2009. Through interviews with 21 public health staff and decision makers, the author sought to investigate how “evidence” was defined by both frontline and management staff and how it was used in decision making. The authors found public health staff, particularly frontline practitioners, to be drawn to grassroots and local “lived experience” evidence. This tacit wisdom, in combination with evidence from academia and clinical evidence accessed through disciplinary or professional networks, offered a knowledge transition opportunity to inform decision making, rather than what can be characterized in the literature as unidirectional knowledge translation. It is often difficult for staff to digest and interpret research as part of their work day because of the volume and density of information that typically counts as evidence. Moreover, there exist challenges to identify and gather indicators as evidence of their work.
When Science, Politics, and Policy Collide: On the Regulation of Anabolic-Androgenic Steroids, Steroid Precursors, and “Dietary Supplements” in the United States
Authors: Denham Bryan E.
Published: January 2011

Twenty years after policy makers passed the Anabolic Steroid Control Act of 1990, adding steroids to the list of Schedule III Controlled Substances in the United States, illicit use of the drugs continues among both adolescents and adults in American society. Some of the men and women who use steroids seek enhanced athletic performance, whereas others simply want to appear more muscular. But what, exactly, is a “steroid”? The present article examines legislation surrounding actual anabolic-androgenic steroids, steroid precursors, and associated “dietary supplements,” exploring how the political interests of policy actors and the economic interests of industry lobbies have compromised regulatory efforts. Among the issues addressed are the arbitrary assignment of substances to (and exemption from) the Omnibus Controlled Substances Act and the retailing of “dietary supplements” that contain widely varying amounts of active ingredients and, in some cases, synthetic steroids. Conceptually, the article draws on the “garbage can” model of policy processes as well as the broader public arenas model of social problems, focusing on subjective issue constructions and symbolic appeals.
Biotechnologies and Human Dignity
Authors: Sweet William , Masciulli Joseph
Published: January 2011

In this article, the authors review some contemporary cases where biotechnologies have been employed, where they have had global implications, and where there has been considerable debate. The authors argue that the concept of dignity, which lies at the center of such documents as the 2005 Universal Declaration on Bioethics and Human Rights, the International Declaration on Human Genetic Data (2003) and the Universal Declaration on the Human Genome and Human Rights (1997) is useful, if not necessary, in engaging in decision making in relation to the moral evaluation of biotechnologies on a global scale.
Regulation in a Brave New World: Safeguarding Against Subversive Threats
Authors: Hornosty Jason
Published: January 2011

Biotechnology is a rapidly advancing science that has the potential to revolutionize medicine and transform human abilities. Accompanying these positives are an underdiscussed category of threats to principles of human rights and equality. Although any technology might be used to inegalitarian ends, biotechnology has the capacity to beget inequality with a genetic basis. Global regulation is needed to safeguard against the subversion of human rights. However, the intangible nature of the risk combined with the medical possibilities of biotechnology present a significant challenge to achieving international consensus on issues of regulation. An inclusive dialogue that builds on the precedent of current global cooperation initiatives is needed to overcome these challenges. Policies need to be based on a comprehensive consideration of biotechnology’s potential impacts. Evaluating whether the proliferation and integration of a technology is desirable for society is more profitable than assessing the technology’s inherent practical or moral value.
The Imperative of Virtue in the Age of Global Technology and Globalized Mass Culture: A Liberal-Humanist Response to the Heideggerian Challenge
Authors: Kowalsky Borys M.
Published: January 2011

How has the globalization of technology contributed to the globalization of the war against the Enlightenment liberal humanism of Western civilization—in particular, to the globalization of the war between religion and science—and with what problematic moral, cultural, and spiritual consequences? Liberal-humanist and Heideggerian perspectives on this issue are considered. The latter is chosen because it constitutes an enduring philosophical and political challenge to liberal humanism. For Heidegger, liberal humanism, far from providing a solution to the problems of global technology, is an inherent part of the problem. A case in point is liberal democracy’s use of technology to produce and purvey a humanly degrading mass culture which it also uses technology to export abroad, in effect, to globalize. The author sets forth a defense of liberal humanism against these criticisms.