Genome-wide association study on dimethylarginines reveals novel AGXT2 variants associated with heart rate variability but not with overall mortality.

AIMS The purpose of this study was to identify novel genetic variants influencing circulating asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels and to evaluate whether they have a prognostic value on cardiovascular mortality. METHODS AND RESULTS We conducted a genome-wide association study on the methylarginine traits and investigated the predictive value of the new discovered variants on mortality. Our meta-analyses replicated the previously known locus for ADMA levels in DDAH1 (rs997251; P = 1.4 × 10(-40)), identified two non-synomyous polymorphisms for SDMA levels in AGXT2 (rs37369; P = 1.4 × 10(-40) and rs16899974; P = 1.5 × 10(-38)) and one in SLC25A45 (rs34400381; P = 2.5 × 10(-10)). We also fine-mapped the AGXT2 locus for further independent association signals. The two non-synonymous AGXT2 variants independently associated with SDMA levels were also significantly related with short-term heart rate variability (HRV) indices in young adults. The major allele (C) of the novel non-synonymous rs16899974 (V498L) variant associated with decreased SDMA levels and an increase in the ratio between the low- and high-frequency spectral components of HRV (P = 0.00047). Furthermore, the SDMA decreasing allele (G) of the non-synomyous SLC25A45 (R285C) variant was associated with a lower resting mean heart rate during the HRV measurements (P = 0.0046), but not with the HRV indices. None of the studied genome-wide significant variants had any major effect on cardiovascular or total mortality in patients referred for coronary angiography. CONCLUSIONS AGXT2 has an important role in SDMA metabolism in humans. AGXT2 may additionally have an unanticipated role in the autonomic nervous system regulation of cardiac function.

EChO

A dedicated mission to investigate exoplanetary atmospheres represents a major milestone in our quest to understand our place in the universe by placing our Solar System in context and by addressing the suitability of planets for the presence of life. EChO—the Exoplanet Characterisation Observatory—is a mission concept specifically geared for this purpose. EChO will provide simultaneous, multi-wavelength spectroscopic observations on a stable platform that will allow very long exposures. The use of passive cooling, few moving parts and well established technology gives a low-risk and potentially long-lived mission. EChO will build on observations by Hubble, Spitzer and ground-based telescopes, which discovered the first molecules and atoms in exoplanetary atmospheres. However, EChO’s configuration and specifications are designed to study a number of systems in a consistent manner that will eliminate the ambiguities affecting prior observations. EChO will simultaneously observe a broad enough spectral region—from the visible to the mid-infrared—to constrain from one single spectrum the temperature structure of the atmosphere, the abundances of the major carbon and oxygen bearing species, the expected photochemically-produced species and magnetospheric signatures. The spectral range and resolution are tailored to separate bands belonging to up to 30 molecules and retrieve the composition and temperature structure of planetary atmospheres. The target list for EChO includes planets ranging from Jupiter-sized with equilibrium temperatures T eq up to 2,000 K, to those of a few Earth masses, with T eq \u223c 300 K. The list will include planets with no Solar System analog, such as the recently discovered planets GJ1214b, whose density lies between that of terrestrial and gaseous planets, or the rocky-iron planet 55 Cnc e, with day-side temperature close to 3,000 K. As the number of detected exoplanets is growing rapidly each year, and the mass and radius of those detected steadily decreases, the target list will be constantly adjusted to include the most interesting systems. We have baselined a dispersive spectrograph design covering continuously the 0.4–16 μm spectral range in 6 channels (1 in the visible, 5 in the InfraRed), which allows the spectral resolution to be adapted from several tens to several hundreds, depending on the target brightness. The instrument will be mounted behind a 1.5 m class telescope, passively cooled to 50 K, with the instrument structure and optics passively cooled to \u223c45 K. EChO will be placed in a grand halo orbit around L2. This orbit, in combination with an optimised thermal shield design, provides a highly stable thermal environment and a high degree of visibility of the sky to observe repeatedly several tens of targets over the year. Both the baseline and alternative designs have been evaluated and no critical items with Technology Readiness Level (TRL) less than 4–5 have been identified. We have also undertaken a first-order cost and development plan analysis and find that EChO is easily compatible with the ESA M-class mission framework.

Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: proposal of an international research group.

BACKGROUND AND PURPOSE To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. METHODS After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. RESULTS Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. CONCLUSIONS Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

The unruptured intracranial aneurysm treatment score: a multidisciplinary consensus.

OBJECTIVE We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. METHODS An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement). RESULTS The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033). CONCLUSIONS This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.

Menos no es siempre más, ni mucho menos = Less isn't always more, not by any means

"Think rationally, but cultivate an artistic sensibility" recommended Henry van de Velde in 1903. This is the direction chosen by three young architects, Marten Claesson, Eero Koivisto and Ola Rune, who have their own practice in Stockholm since 1993. Architects, interior designers, furniture designers and teachers, they entered the professional world with Vila Wabi, an elongated box, temporarily set into the Sergel square (Stockholm), designed to house a family of four. Since then, they have designed a big number of shops, showrooms, bars and restaurants, offices and houses mostly in Sweden but also abroad. Despite an international outlook and appeal the practice makes part of an ongoing tradition of Scandinavian design.

CLIMA ORGANIZACIONAL E BURNOUT: UM ESTUDO COM SERVIDORES PÚBLICOS FEDERAIS

As condições inadequadas vivenciadas nas organizações afligem não só os trabalhadores da iniciativa privada, pois são igualmente encontradas no segmento estatal, contrariando a expectativa de que o aparato governamental eliminaria as condições insalubres e criaria outras melhores nas quais prevalecesse à promoção de saúde. Diante desse panorama questionou-se porque, uma vez que, pelo menos do ponto de vista da sociedade leiga, esses servidores estão submetidos a condições privilegiadas de trabalho. O presente estudo objetivou identificar e descrever possíveis relações entre o clima organizacional e o burnout em servidores públicos de uma instituição federal de ensino. Objetivou-se ainda descrever o clima organizacional predominante. A pesquisa realizada teve cunho quantitativo, tipo estudo de caso e exploratória. A coleta de dados deu-se por meio das escalas ECO (escala de clima organizacional), ECB (escala de caracterização do burnout) e um questionário sociodemográfico, todos os instrumentos autoaplicáveis eletronicamente disponíveis à instituição. Participaram do estudo 201 servidores públicos federais, com idade média de 37 anos, majoritariamente de nível superior e casados. Os resultados revelaram que cerca de um quarto dos participantes raramente experimentaram burnout, no entanto outra quarta parte deles frequentemente experimentaram altos níveis de burnout, resultado bastante expressivo. Os servidores perceberam clima organizacional mediano, destacando-se a boa coesão entre os colegas de trabalho e a percepção de baixa recompensa. Merece destaque a grande dispersão entre as percepções de clima, o que permite inferir haver subclimas não identificados nesta investigação, possivelmente ocasionados por uma força de clima fraca e pela participação dos servidores de unidades de ensino geograficamente distintas, geridas por gestores locais com relativa autonomia. Os resultados dos cálculos de correlação revelaram que, quanto menos os participantes percebem apoio da chefia e da organização, coesão entre colegas, e mais controle/pressão, mais exaustos se sentem, mais desumanizam as pessoas com quem tratam e mais se decepcionam no trabalho e vice-versa. Conforto físico menor está associado a maior desumanização e a mais decepção no trabalho e vice-versa; e que controle/pressão, relaciona-se positiva e fracamente com desumanização e vice-versa. Desta forma, a hipótese de que existe associação entre burnout e clima organizacional foi confirmada. Os resultados também revelaram que os servidores com burnout, perceberam pior clima organizacional que os seus pares sem burnout, confirmando a segunda hipótese. Esses servidores também se mostraram neutros quanto à percepção de apoio da chefia e conforto físico; não percebem controle pressão, nem recompensa; todavia percebem coesão entre os colegas. Esses resultados sugerem que os participantes têm se apoiado nessas relações para suportar a indiferença e ausência de estímulos experimentados no trabalho. Os resultados obtidos nesse estudo permitiram concluir que o clima organizacional é fraco, provavelmente influenciado por uma cultura organizacional fraca, explicando a heterogeneidade da percepção do clima organizacional pelos servidores. Além disso, embora haja burnout entre poucos participantes, há que se atentar que cerca de um quarto deles, encontra-se acometido desta síndrome e isto poderá contagiar os demais.

ANX7, a candidate tumor suppressor gene for prostate cancer

The ANX7 gene is located on human chromosome 10q21, a site long hypothesized to harbor a tumor suppressor gene(s) (TSG) associated with prostate and other cancers. To test whether ANX7 might be a candidate TSG, we examined the ANX7-dependent suppression of human tumor cell growth, stage-specific ANX7 expression in 301 prostate specimens on a prostate tissue microarray, and loss of heterozygosity (LOH) of microsatellite markers at or near the ANX7 locus. Here we report that human tumor cell proliferation and colony formation are markedly reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell lines, LNCaP and DU145. Consistently, analysis of ANX7 protein expression in human prostate tumor microarrays reveals a significantly higher rate of loss of ANX7 expression in metastatic and local recurrences of hormone refractory prostate cancer as compared with primary tumors (P = 0.0001). Using four microsatellite markers at or near the ANX7 locus, and laser capture microdissected tumor cells, 35% of the 20 primary prostate tumors show LOH. The microsatellite marker closest to the ANX7 locus showed the highest rate of LOH, including one homozygous deletion. We conclude that the ANX7 gene exhibits many biological and genetic properties expected of a TSG and may play a role in prostate cancer progression.

Electrochemical reactions of catechol, methylcatechol and dopamine at tetrahedral amorphous carbon (ta-C) thin film electrodes

The electrochemical reactions of dopamine, catechol and methylcatechol were investigated at tetrahedral amorphous carbon (ta-C) thin film electrodes. In order to better understand the reaction mechanisms of these molecules, cyclic voltammetry with varying scan rates was carried out at different pH values in H2SO4 and PBS solutions. The results were compared to the same redox reactions taking place at glassy carbon (GC) electrodes. All three catechols exhibited quasi-reversible behavior with sluggish electron transfer kinetics at the ta-C electrode. At neutral and alkaline pH, rapid coupled homogeneous reactions followed the oxidation of the catechols to the corresponding o-quinones and led to significant deterioration of the electrode response. At acidic pH, the extent of deterioration was considerably lower. All the redox reactions showed significantly faster electron transfer kinetics at the GC electrode and it was less susceptible toward surface passivation. An EC mechanism was observed for the oxidation of dopamine at both ta-C and GC electrodes and the formation of polydopamine was suspected to cause the passivation of the electrodes.

Sense of coherence and diabetes:a prospective occupational cohort

Background: Sense of coherence (SOC) is an individual characteristic related to a positive life orientation leading to effective coping. A weak SOC has been associated with indicators of general morbidity and mortality. However, the relationship between SOC and diabetes has not been studied in prospective design. The present study prospectively examined the relationship between a weak SOC and the incidence of diabetes. Methods: The relationship between a weak SOC and the incidence of diabetes was investigated among 5827 Finnish male employees aged 18–65 at baseline (1986). SOC was measured by questionnaire survey at baseline. Data on prescription diabetes drugs from 1987 to 2004 were obtained from the Drug Imbursement Register held by the Social Insurance Institution. Results: During the follow-up, 313 cases of diabetes were recorded. A weak SOC was associated with a 46% higher risk of diabetes in participants who had been =<50 years of age on entry into the study. This association was independent of age, education, marital status, psychological distress, self-rated health, smoking status, binge drinking and physical activity. No similar association was observed in older employees. Conclusion: The results suggest that besides focusing on well-known risk factors for diabetes, strengthening SOC in employees of =<50 years of age can also play a role in attempts to tackle increasing rates of diabetes.

Teaching Intercultural Competence in Translator Training

In this position paper we define an interculturally competent translator as one that demonstrates a high level of intercultural knowledge, skills, attitude and flexibility throughout his or her professional engagements. We argue that to attain this goal in translator training intercultural competence needs to be introduced into the curriculum explicitly and in a conceptually clear manner. In this article we provide an overview of earlier attempts at discussing the role of intercultural communication in translator training curricula and we discuss the various pedagogical and practical challenges involved. We also look at some future challenges, identifying increasing societal diversity as both a source of added urgency into intercultural training and a challenge for traditional biculturally based notions of translators’ intercultural competence and we argue for the central role of empathy. Finally, and importantly, we introduce the contributions to the special issue.