Habitual energy expenditure modifies the association between NOS3 gene polymorphisms and blood pressue

BACKGROUND: The endothelial nitric-oxide synthase (NOS3) gene encodes the enzyme (eNOS) that synthesizes the molecule nitric oxide, which facilitates endothelium-dependent vasodilation in response to physical activity. Thus, energy expenditure may modify the association between the genetic variation at NOS3 and blood pressure. METHODS: To test this hypothesis, we genotyped 11 NOS3 polymorphisms, capturing all common variations, in 726 men and women from the Medical Research Council (MRC) Ely Study (age (mean +/- s.d.): 55 +/- 10 years, body mass index: 26.4 +/- 4.1 kg/m(2)). Habitual/non-resting energy expenditure (NREE) was assessed via individually calibrated heart rate monitoring over 4 days. RESULTS: The intronic variant, IVS25+15 [G-->A], was significantly associated with blood pressure; GG homozygotes had significantly lower levels of diastolic blood pressure (DBP) (-2.8 mm Hg; P = 0.016) and systolic blood pressure (SBP) (-1.9 mm Hg; P = 0.018) than A-allele carriers. The interaction between NREE and IVS25+15 was also significant for both DBP (P = 0.006) and SBP (P = 0.026), in such a way that the effect of the GG-genotype on blood pressure was stronger in individuals with higher NREE (DBP: -4.9 mm Hg, P = 0.02. SBP: -3.8 mm Hg, P= 0.03 for the third tertile). Similar results were observed when the outcome was dichotomously defined as hypertension. CONCLUSIONS: In summary, the NOS3 IVS25+15 is directly associated with blood pressure and hypertension in white Europeans. However, the associations are most evident in the individuals with the highest NREE. These results need further replication and have to be ideally tested in a trial before being informative for targeted disease prevention. Eventually, the selection of individuals for lifestyle intervention programs could be guided by knowledge of genotype.

A Kind of Integrity: explorations in history and drama

All of our knowledge of history is mediated in one way or another. Even the experience of first hand witnesses are, it may be argued, subject to semiotic influences such as physical and emotional position, attitudinal point of view and accuracy of recall. A great deal of historical knowledge is acquired through dramatised versions of historical events. As the characters who actually took part in historical events become the dramatis personae of re-enacted accounts, their stories are edited not only to meet dramatic necessities but the social, psychological and cultural needs of both storytellers and audience. The process of popularising history in this way thus becomes as much about the effects of events on people as the events themselves. This chapter describes and analyses the way in which four historical events have formed the basis of school based drama workshops that explore this process. The Player in Tom Stoppard’s ‘Rosencrantz and Guildenstern Are Dead’ posits that actors do on stage what others are supposed to do off, which, he claims, ‘is a kind of integrity.’ The chapter discusses how drama may be used to explore not only stories from history but how those stories may be mediated and so become open to multiple interpretations. The process of dramatising events from history provides opportunities to develop and exercise a critical literacy that is concerned not so much with either fact or empathy as with interrogating both why and how stories are told. Thus, the experience of exploring the symbiotic relationship between drama and history is dependent on an internal logic which may indeed be perceived as a kind of integrity.

Global monsoons in the mid-Holocene and oceanic feedback

The response of the six major summer monsoon systems (the North American monsoon, the northern Africa monsoon, the Asia monsoon, the northern Australasian monsoon, the South America monsoon and the southern Africa monsoon) to mid-Holocene orbital forcing has been investigated using a coupled ocean–atmosphere general circulation model (FOAM), with the focus on the distinct roles of the direct insolation forcing and oceanic feedback. The simulation result is also found to compare well with the NCAR CSM. The direct effects of the change in insolation produce an enhancement of the Northern Hemisphere monsoons and a reduction of the Southern Hemisphere monsoons. Ocean feedbacks produce a further enhancement of the northern Africa monsoon and the North American monsoon. However, ocean feedbacks appear to weaken the Asia monsoon, although the overall effect (direct insolation forcing plus ocean feedback) remains a strengthened monsoon. The impact of ocean feedbacks on the South American and southern African monsoons is relatively small, and therefore these regions, especially the South America, experienced a reduced monsoon regime compared to present. However, there is a strong ocean feedback on the northern Australian monsoon that negates the direct effects of orbital changes and results in a strengthening of austral summer monsoon precipitation in this region. A new synthesis is made for mid-Holocene paleoenvironmental records and is compared with the model simulations. Overall, model simulations produce changes in regional climates that are generally consistent with paleoenvironmental observations.

Association between Mediterranean and Nordic diet scores and changes in weight and waist circumference: influence of FTO and TCF7L2 loci

BACKGROUND: Several studies have shown that adherence to the Mediterranean Diet measured by using the Mediterranean diet score (MDS) is associated with lower obesity risk. The newly proposed Nordic Diet could hold similar beneficial effects. Because of the increasing focus on the interaction between diet and genetic predisposition to adiposity, studies should consider both diet and genetics. OBJECTIVE: We investigated whether FTO rs9939609 and TCF7L2 rs7903146 modified the association between the MDS and Nordic diet score (NDS) and changes in weight (Δweight), waist circumference (ΔWC), and waist circumference adjusted for body mass index (BMI) (ΔWCBMI). DESIGN: We conducted a case-cohort study with a median follow-up of 6.8 y that included 11,048 participants from 5 European countries; 5552 of these subjects were cases defined as individuals with the greatest degree of unexplained weight gain during follow-up. A randomly selected subcohort included 6548 participants, including 5496 noncases. Cases and noncases were compared in analyses by using logistic regression. Continuous traits (ie, Δweight, ΔWC, and ΔWCBMI) were analyzed by using linear regression models in the random subcohort. Interactions were tested by including interaction terms in models. RESULTS: A higher MDS was significantly inversely associated with case status (OR: 0.98; 95% CI: 0.96, 1.00), ΔWC (β = -0.010 cm/y; 95% CI: -0.020, -0.001 cm/y), and ΔWCBMI (β = -0.008; 95% CI:-0.015, -0.001) per 1-point increment but not Δweight (P = 0.53). The NDS was not significantly associated with any outcome. There was a borderline significant interaction between the MDS and TCF7L2 rs7903146 on weight gain (P = 0.05), which suggested a beneficial effect of the MDS only in subjects who carried 1 or 2 risk alleles. FTO did not modify observed associations. CONCLUSIONS: A high MDS is associated with a lower ΔWC and ΔWCBMI, regardless of FTO and TCF7L2 risk alleles. For Δweight, findings were less clear, but the effect may depend on the TCF7L2 rs7903146 variant. The NDS was not associated with anthropometric changes during follow-up.

Culture, compassion and clinical neglect: probity in the NHS after Mid Staffordshire

Speaking of the public response to the deaths of children at the Bristol Royal Infirmary before 2001, the BMJ commented that the NHS would be 'all changed, changed utterly'. Today, two inquiries into the Mid Staffordshire Foundation Trust suggest nothing changed at all. Many patients died as a result of their care and the stories of indifference and neglect there are harrowing. Yet Bristol and Mid Staffordshire are not isolated reports. In 2011, the Health Services Ombudsman reported on the care of elderly and frail patients in the NHS and found a failure to recognise their humanity and individuality and to respond to them with sensitivity, compassion and professionalism. Likewise, the Care Quality Commission and Healthcare Commission received complaints from patients and relatives about the quality of nursing care. These included patients not being fed, patients left in soiled bedding, poor hygiene practices, and general disregard for privacy and dignity. Why is there such tolerance of poor clinical standards? We need a better understanding of the circumstances that can lead to these outcomes and how best to respond to them. We discuss the findings of these and other reports and consider whether attention should be devoted to managing individual behaviour, or focus on the systemic influences which predispose hospital staff to behave in this way. Lastly, we consider whether we should look further afield to cognitive psychology to better understand how clinicians and managers make decisions?

What is outside? The early years foundation stage in England: outdoor facilities, organisation and staff attitudes

The purpose of this paper is to report on the facilities available, organisation of, and staff attitudes to early years outdoor education from schools within the south east of England, focusing on provision for children aged three to five. One component of the successful education of the child involves providing an ‘environment for learning’, including the facilities, layout and routines. This paper presents findings concerning the type and variety of facilities available outside; the various styles of organisation of the space; staff attitudes about: their roles, their aims for the environment, children’s behaviour and learning, and perceived drawbacks to practice. This paper draws on empirical data collected from schools within the University of Reading partnership. The findings suggest that although all early years settings must adhere to the statutory framework there are a range of facilities available, and there are a number of ways this environment is organised. Further there appears to be uncertainty about the adult role outside and the aims for activities. The conclusions drawn indicate that staff do not appear to be linking their aims for outdoor education to the facilities provided or to their actions outside. This means there is not a clear link between what staff provide outside and the declared ambitions for learning. This study is important as all educators need to be certain about their aims for education to ensure best outcomes for children. The implications of these findings for early years teachers are that they need to be able to articulate their aims for outdoor education and to provide the correct facilities to achieve these aims. Finally this study was undertaken to raise debate, posit questions and to ascertain the parameters for further research about the early years outdoor environment.

Information customization and food choice

In this paper we employ a hypothetical discrete choice experiment (DCE) to examine how much consumers are willing to pay to use technology to customize their food shopping. We conjecture that customized information provision can aid in the composition of a healthier shop. Our results reveal that consumers are prepared to pay relatively more for individual specic information as opposed to generic nutritional information that is typically provided on food labels. In arriving at these results we have examined various model specications including those that make use of ex-post de-brieng questions on attribute nonattendance and attribute ranking information and those that consider the time taken to complete the survey. Our main results are robust to the various model specications we examine

Human gut microbiota and its relationship to health and disease

Probiotics are live microorganisms that confer a health benefit on the host when administered in appropriate amounts. Over 700 randomized, controlled, human studies have been conducted with probiotics thus far, with the results providing strong support for the use of probiotics in the clinical prevention or treatment of gastrointestinal tract disorders and metabolic syndrome. The present review is based on webinar presentations that were developed by the American Gastroenterological Association (AGA) in partnership with the International Scientific Association for Probiotics and Prebiotics (ISAPP) and the North American branch of the International Life Sciences Institute (ILSI North America). The presentations provided gastroenterologists and researchers with fundamental and current scientific information on the influence of gut microbiota on human health and disease, as well as clinical intervention strategies and practical guidelines for the use of probiotics and prebiotics.

Soft balancing in the Americas: Latin American opposition to U.S. intervention, 1898–1936

In the aftermath of the 2003 U.S.-led invasion of Iraq, scholars of international relations debated how to best characterize the rising tide of global opposition. The concept of “soft balancing” emerged as an influential, though contested, explanation of a new phenomenon in a unipolar world: states seeking to constrain the ability of the United States to deploy military force by using multinational organizations, international law, and coalition building. Soft balancing can also be observed in regional unipolar systems. Multinational archival research reveals how Argentina, Mexico, and other Latin American countries responded to expanding U.S. power and military assertiveness in the early twentieth century through coordinated diplomatic maneuvering that provides a strong example of soft balancing. Examination of this earlier case makes an empirical contribution to the emerging soft-balancing literature and suggests that soft balancing need not lead to hard balancing or open conflict.

Population-Based Multicentric Survey of Hepatitis B Infection and Risk Factor Differences among Three Regions in Brazil

This multicentric population-based study in Brazil is the first national effort to estimate the prevalence of hepatitis B (HBV) and risk factors in the capital cities of the Northeast. Central-West, and Federal Districts (2004-2005). Random multistage cluster sampling was used to select persons 13-69 years of age. Markers for HBV were tested by enzyme-linked immunosorbent assay. The HBV genotypes were determined by sequencing hepatitis B surface antigen (HBsAg). Multivariate analyses and simple catalytic model were performed. Overall. 7,881 persons were inculded < 70% were not vaccinated. Positivity for HBsAg was less than 1% among non-vaccinated persons and genotypes A, D, and F co-circulated. The incidence of infection increased with age with similar force of infection in all regions. Males and persons having initiated sexual activity were associated with HBV infection in the two settings: healthcare jobs and prior hospitalization were risk factors in the Federal District. Our survey classified these regions as areas with HBV endemicity and highlighted the risk factors differences among the settings.

Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression

Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variations in myocardial biology. We, therefore, generated a cardiomyocyte-specific circadian clock mutant (CCM) mouse to test this hypothesis. At 12 wk of age, CCM mice exhibit normal myocardial contractile function in vivo, as assessed by echocardiography. Radiotelemetry studies reveal attenuation of heart rate diurnal variations and bradycardia in CCM mice (in the absence of conduction system abnormalities). Reduced heart rate persisted in CCM hearts perfused ex vivo in the working mode, highlighting the intrinsic nature of this phenotype. Wild-type, but not CCM, hearts exhibited a marked diurnal variation in responsiveness to an elevation in workload (80 mmHg plus 1 mu M epinephrine) ex vivo, with a greater increase in cardiac power and efficiency during the dark (active) phase vs. the light (inactive) phase. Moreover, myocardial oxygen consumption and fatty acid oxidation rates were increased, whereas cardiac efficiency was decreased, in CCM hearts. These observations were associated with no alterations in mitochondrial content or structure and modest mitochondrial dysfunction in CCM hearts. Gene expression microarray analysis identified 548 and 176 genes in atria and ventricles, respectively, whose normal diurnal expression patterns were altered in CCM mice. These studies suggest that the cardiomyocyte circadian clock influences myocardial contractile function, metabolism, and gene expression.

Att tillämpa återkommande mätning av kundnöjdhet i IT-projekt : En vidareutvecklad modell baserad på modellerna American Customer Satisfaction Index (ACSI) och SERVQUAL

I dagens samhälle är det allt viktigare för företag att behålla sina existerande kunder då konkurrensen blir allt hårdare. Detta medför att företag försöker vidta åtgärder för att vårda relationer med sina kunder. Detta problem är även högst relevant inom IT-branschen. Inom IT-branschen är det vanligt att arbeta agilt i IT-projekt. Vår samarbetspartner har sett ett ökat behov av att mäta servicekvalitet på ett återkommande sätt inom IT-projekt, detta för att mäta relevanta variabler som sträcker sig utanför kravspecifikationen. För att mäta framgång gällande detta arbetssätt vill man kunna mäta Nöjd Kund Index (NKI) för att kunna jämföra IT-projekt internt i företaget. Då tidigare forskning visat avsaknad av modeller innehållande både mätning av servicekvalitet samt NKI har lämplig litteratur studerats där det framkommit att modellen SERVQUAL är vedertagen för mätning av servicekvalitet och modellen American Customer Satisfaction Index (ACSI) är vedertagen för mätning av NKI. Detta har legat till grund för arbetets problemformulering och syfte. Syftet med arbetet är att skapa en vidareutvecklad modell för mätning av NKI för att jämföra IT-projekt internt samt återkommande mätning av servicekvalitet inom IT-projekt. Framtagande av denna modell har sedan skett genom forskningsstrategin Design and Creation. Intervjuer har genomförts för kravfångst till den vidareutvecklade modellen. Resultatet av denna forskningsstrategi blev sedan en vidareutvecklad modell baserad på ovan nämnda modeller med återkommande förhållningssätt för mätning av servicekvalitet inom IT-projekt och mätning av NKI för att jämföra IT-projekt internt i företaget. Den framtagna modellen har sedan verifierats genom ytterligare intervjuer med respondenter som innehar god erfarenhet från kundsidan av IT-projekt. Från dessa intervjuer kunde sedan slutsats dras att denna modell är att anse som applicerbar i empirin gällande IT-projekt.

Dwelling in possibility: aestheticizing identity in African American women's fiction

African American women writers define aesthetics through their negotiation of identity in the politicized loci of space, place and voice. In the balkanization of such issues of voice and space, we can see the ways that the emergent selfis embodied and aestheticized in literature. To do so creates a more tactile and "artfull" representation of the self rather than a representation of identity as a mere abstract concept. To use written language to express the self is to carry processes of selfdefinition for black women into the realm of creative production. For women, especially black women, who are a politically and socially compromised element of society, the written word is a way of expressing the politically and the socially critical voice that is suppressed in other forums of expression. Using theories on "writing in difference" as a skeleton key, this project seeks to outline some of the ways that black women writers use aesthetic elements in their art to express the potential for self-examination, discovery, and emancipation.

Simulation -based smoothing and filtering in factor stochastic volatility models : two econometric applications (July-2001)

The past decade has wítenessed a series of (well accepted and defined) financial crises periods in the world economy. Most of these events aI,"e country specific and eventually spreaded out across neighbor countries, with the concept of vicinity extrapolating the geographic maps and entering the contagion maps. Unfortunately, what contagion represents and how to measure it are still unanswered questions. In this article we measure the transmission of shocks by cross-market correlation\ coefficients following Forbes and Rigobon's (2000) notion of shift-contagion,. Our main contribution relies upon the use of traditional factor model techniques combined with stochastic volatility mo deIs to study the dependence among Latin American stock price indexes and the North American indexo More specifically, we concentrate on situations where the factor variances are modeled by a multivariate stochastic volatility structure. From a theoretical perspective, we improve currently available methodology by allowing the factor loadings, in the factor model structure, to have a time-varying structure and to capture changes in the series' weights over time. By doing this, we believe that changes and interventions experienced by those five countries are well accommodated by our models which learns and adapts reasonably fast to those economic and idiosyncratic shocks. We empirically show that the time varying covariance structure can be modeled by one or two common factors and that some sort of contagion is present in most of the series' covariances during periods of economical instability, or crisis. Open issues on real time implementation and natural model comparisons are thoroughly discussed.

Do equity and foreign currency risk premiums display common patterns?

In da Costa et al. (2006) we have shown how a same pricing kernel can account for the excess returns of the S&:P500 over the US short term bond and of the uncovered over the covered trading of foreign government bonds. In this paper we estimate and test the overidentifying restrictiom; of Euler equations associated with "ix different versions of the Consumption Capital Asset Pricing I\Iodel. Our main finding is that the same (however often unreasonable) values for the parameters are estimated for ali models in both nmrkets. In most cases, the rejections or otherwise of overidentifying restrictions occurs for the two markets, suggesting that success and failure stories for the equity premium repeat themselves in foreign exchange markets. Our results corroborate the findings in da Costa et al. (2006) that indicate a strong similarity between the behavior of excess returns in the two markets when modeled as risk premiums, providing empirical grounds to believe that the proposed preference-based solutions to puzzles in domestic financiaI markets can certainly shed light on the Forward Premium Puzzle.