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

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

A Spherical Compound Refraktive Lens to Control X-Ray Beams

Compound refractive X-ray lens, consisting of a lot number of placed in-line concave microlenses. is a unique device to control X-ray beams

OVA-LEAK: Prognostic score for colo-rectal anastomotic leakage in patients undergoing ovarian cancer surgery

Objective: The objective of the present study was to define and validate an anastomotic leak prognostic score based on previously described and reported anastomotic leak risk factors (OVA-LEAK: https://n9.cl/ova-leakscore) and to establish if the use of OVA-LEAK score is better than clinical criteria (surgeon's choice) selecting anastomosis to be protected with a diverting ileostomy. Material &amp; methods: This is a retrospective, multicentre cohort study that included patients who underwent cytoreductive surgery for primary advanced or relapsed ovarian cancer with colorectal resection and anastomosis between January 2011 and June 2021. Data from patients already included in the previous predictive model were not considered in the present analysis. To validate the performance of our logistic regression model, we used the OVA-LEAK formula (Annex I: https://n9.cl/ova-leakscore) for estimating leakage probabilities in a new independent cohort. Then, receiver operating characteristic (ROC) analysis was performed and area under the curve (AUC) was used to measure the performance of the model. Additionally, the Brier score was also estimated. 95% confidence intervals (CI) for each of the estimated performance measures were also calculated. Results: 848 out of 1159 recruited patients were finally included in the multivariable logistic regression model validation. The AUC of the new cohort was 0.63 for predicting anastomotic leak. Considering a cut-off point of 22.1% to be ‘positive’ (to get a leak) this would provide a sensitivity of 0.45, specificity of 0.80, positive predictive value of 0.09 and negative predictive value of 0.97 for anastomotic leak. If we consider this cut-off point to select patients at risk of leak for bowel diversion, up to 22.5% of the sampled patients would undergo a diverting ileostomy and 47% (18/40) of the anastomotic leaks would be ‘protected’ with the stoma. Nevertheless, if we consider only the ‘clinical criteria’ for performing or not a diverting ileostomy, only 12.5% (5/40) of the leaks would be ‘protected’ with a stoma, with a rate of diverting ileostomy of up to 24.3%. Conclusions: Compared with subjective clinical criteria, the use of a predictive model for anastomotic leak improves the selection of patients who would benefit from a diverting ileostomy without increasing the rate of stoma use