Polymorphisms in the WNK1 gene are asociated with blood pressure variation and urinary potassium excretion

WNK1 - a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control - is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23–4.9), DBP 1.9 mmHg (95%CI:0.7–3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0–1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7×10−3, combined with BRIGHT data-set p = 2×10−4, n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p10 mmHg reduction) and risk for hypertension (OR<0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH

Shaping policy development in a UK Government department

Policy-making organisations are often accused of linear and narrow-focused thinking and de-cision-making, failing to account for the diversity of human needs and goals, even the diversity of goals existing across different government departments. Accordingly, resulting government policies can be fragmented and do not account for the mul-tiple aspects important for human wellbeing. As unintended consequences arise across a broad range of outcomes, an integrated, system-wide and participatory approach to policy-making is needed. It needs to shape thinking around policy-making to interlink the different individuals and organisations interacting with these policies. This paper suggests a participatory systems approach that engages diverse policy-makers in a process of co-creation and shared learning. Instead of focusing on narrow policy develop-ment, it develops a process fuelled by systems thinking and participatory system dynamics modelling to shape policy-making. It refers to a collaboration with a UK government depart-ment and takes policy-making about domestic heating energy from a home-owner and market perspective as an example. The collaborative approach uses interviews, workshops, qualita-tive mapping, causal loop diagramming and simulation modelling to jointly establish causal maps of nonlinearities, complex interrelationships and feedback processes in the area of do-mestic heating energy efficiency and use. The collaborative project shows that interest in systems thinking can be triggered through a participatory research project and interaction with a simulation environment. It also presents a process for engaging collaborators with different interdisciplinary background and discusses challenges and successes. Finally it reveals how participants unfamiliar to systems thinking can engage in a new way of thinking and collaborating. System dynamics modelling, systems thinking, home energy efficiency, retrofit, home-owner decision-makin

Avaliação de ciclo de vida de fertilizantes: fase de uso.

O Brasil é o quarto maior consumidor de fertilizantes do mundo e atualmente importa mais da metade da sua demanda. Fertilizantes ou práticas de manejo inadequados resultam em grandes perdas de nutrientes para o ambiente, o que gera prejuízos econômicos e impactos ambientais. Ferramentas de gestão ambiental, como a Avaliação de Ciclo de Vida, podem ser usadas para se estimar esses impactos. O presente estudo, desenvolvido no âmbito do projeto FertBrasil, da Embrapa, adota a abordagem da Avaliação do Ciclo de Vida para avaliar os impactos ambientais potenciais de diferentes fertilizantes nitrogenados na sua etapa de uso, neste caso aplicados à cultura do milho. As etapas anteriores, de produção destes insumos, serão adequadas às condições brasileiras na sequência deste trabalho. Os fertilizantes nitrogenados comparados foram: a) ureia; b) ureia em mistura com zeólita; c) sulfato de amônio; e d) nitrato de cálcio ? aplicados em adubação de cobertura, na dose de 120 kg N ha-1. Foram estimadas as emissões de gases de efeito estufa e as emissões derivadas da combustão do óleo diesel em operações agrícolas. O desempenho ambiental do milho cultivado sob diferentes fontes de nitrogênio foi grandemente influenciado pela produtividade agrícola e pela quantidade de fertilizante nitrogenado aportado ao sistema produtivo. A etapa de produção dos fertilizantes também foi muito impactante, considerando-se o completo ciclo de vida do produto. O nitrato de cálcio foi o fertilizante de cobertura que apresentou o pior desempenho ambiental, sendo o mais impactante em sete, das dez categorias de impacto analisadas

Prevalence of diabetes mellitus and the performance of a risk score among Hindustani Surinamese, African Surinamese and ethnic Dutch: a cross-sectional population-based study

<p>Abstract</p> <p>Background</p> <p>While the prevalence of type 2 diabetes mellitus (DM) is high, tailored risk scores for screening among South Asian and African origin populations are lacking. The aim of this study was, first, to compare the prevalence of (known and newly detected) DM among Hindustani Surinamese, African Surinamese and ethnic Dutch (Dutch). Second, to develop a new risk score for DM. Third, to evaluate the performance of the risk score and to compare it to criteria derived from current guidelines.</p> <p>Methods</p> <p>We conducted a cross-sectional population based study among 336 Hindustani Surinamese, 593 African Surinamese and 486 Dutch, aged 35–60 years, in Amsterdam. Logistic regressing analyses were used to derive a risk score based on non-invasively determined characteristics. The diagnostic accuracy was assessed by the area under the Receiver-Operator Characteristic curve (AUC).</p> <p>Results</p> <p>Hindustani Surinamese had the highest prevalence of DM, followed by African Surinamese and Dutch: 16.7, 8.1, 4.2% (age 35–44) and 35.0, 19.0, 8.2% (age 45–60), respectively. The risk score included ethnicity, body mass index, waist circumference, resting heart rate, first-degree relative with DM, hypertension and history of cardiovascular disease. Selection based on age alone showed the lowest AUC: between 0.57–0.62. The AUC of our score (0.74–0.80) was higher than that of criteria from guidelines based solely on age and BMI and as high as criteria that required invasive specimen collection.</p> <p>Conclusion</p> <p>In Hindustani Surinamese and African Surinamese populations, screening for DM should not be limited to those over 45 years, as is advocated in several guidelines. If selective screening is indicated, our ethnicity based risk score performs well as a screening test for DM among these groups, particularly compared to the criteria based on age and/or body mass index derived from current guidelines.</p

How Stable are Monetary Models of the Dollar-Euro Exchange Rate? A Time-Varying Coefficient Approach

This paper examines the significance of different fundamental regimes by applying various monetary models of the exchange rate to one of the politically most important exchange rates, the exchange rate of the US dollar vis-à-vis the euro (the DM). We use monthly data from 1975:01 to 2007:12. Applying a novel time-varying coefficient estimation approach, we come up with interesting properties of our empirical models. First, there is no stable long-run equilibrium relationship among fundamentals and exchange rates since the breakdown of BrettonWoods. Second, there are no recurring regimes, i.e. across different regimes either the coefficient values for the same fundamentals differ or the significance differs. Third, there is no regime in which no fundamentals enter. Fourth, the deviations resulting from the stepwise cointegrating relationship act as a significant error-correction mechanism. In other words, we are able to show that fundamentals play an important role in determining the exchange rate although their impact differs significantly across different subperiods