White cell count in the normal range and short-term and long-term mortality: international comparisons of electronic health record cohorts in England and New Zealand

OBJECTIVES: Electronic health records offer the opportunity to discover new clinical implications for established blood tests, but international comparisons have been lacking. We tested the association of total white cell count (WBC) with all-cause mortality in England and New Zealand. SETTING: Primary care practices in England (ClinicAl research using LInked Bespoke studies and Electronic health Records (CALIBER)) and New Zealand (PREDICT). DESIGN: Analysis of linked electronic health record data sets: CALIBER (primary care, hospitalisation, mortality and acute coronary syndrome registry) and PREDICT (cardiovascular risk assessments in primary care, hospitalisations, mortality, dispensed medication and laboratory results). PARTICIPANTS: People aged 30-75 years with no prior cardiovascular disease (CALIBER: N=686 475, 92.0% white; PREDICT: N=194 513, 53.5% European, 14.7% Pacific, 13.4% Maori), followed until death, transfer out of practice (in CALIBER) or study end. PRIMARY OUTCOME MEASURE: HRs for mortality were estimated using Cox models adjusted for age, sex, smoking, diabetes, systolic blood pressure, ethnicity and total:high-density lipoprotein (HDL) cholesterol ratio. RESULTS: We found 'J'-shaped associations between WBC and mortality; the second quintile was associated with lowest risk in both cohorts. High WBC within the reference range (8.65-10.05×10(9)/L) was associated with significantly increased mortality compared to the middle quintile (6.25-7.25×10(9)/L); adjusted HR 1.51 (95% CI 1.43 to 1.59) in CALIBER and 1.33 (95% CI 1.06 to 1.65) in PREDICT. WBC outside the reference range was associated with even greater mortality. The association was stronger over the first 6 months of follow-up, but similar across ethnic groups. CONCLUSIONS: Clinically recorded WBC within the range considered 'normal' is associated with mortality in ethnically different populations from two countries, particularly within the first 6 months. Large-scale international comparisons of electronic health record cohorts might yield new insights from widely performed clinical tests. TRIAL REGISTRATION NUMBER: NCT02014610

Genetic control of resistance to gastro-intestinal parasites in crossbred cashmere-producing goats: responses to selection, genetic parameters and relationships with production traits

AbstractThis paper investigates the genetic control of the resistance of goats to nematode parasites, and relationships between resistance and production traits. The data set comprised faecal egg counts (FECs) measured on 830 naturally challenged (predominant species Teladorsagia circumcincta), crossbred cashmere-producing goats over 5 years (1993-1997) and production traits (fibre traits and live weight) on 3100 goats from the same population in Scotland, over 11 years (1987-1997). Egg counts comprised repeated measurements (4 to 11) taken at 12 to 18 months of age and production traits, i.e. live weight and fibre traits, were measured at approximately 5 months of age. The goats for which FECs were available were subdivided into a line selected for decreased FECs, using the geometric mean FEC across the measurement period and goats not selected on the basis of FECs, acting as controls. The selected line had significantly lower FECs, compared with the control, in 4 out of 5 years (back transformed average proportional difference of 0·23). The heritability of a single FEC measurement (after cubic root transformation) was 0·17 and the heritability of the mean FEC was 0·32. The heritabilities of the fibre traits were moderate to high with the majority in excess of 0·5. The heritability of live weight was 0·22. Genetic correlations between FECs and production traits were slightly positive but not significantly different from zero. Phenotypic and environmental correlations were very close to zero with the environmental correlations always being negative. It is concluded that selection for reduced FEC is possible for goats. Benefits of such selection will be seen when animals are kept for more than 1 year of productive life.</jats:p

Perceived non-smoking norms and motivation to stop smoking, quit attempts, and cessation: a cross-sectional study in England

This study examined the prevalence of non-smoking norms in England and their associations with motivation to stop smoking, quit attempts, and cessation. Data were from a representative cross-sectional survey of 1,521 adults (301 combustible tobacco smokers). Descriptive non-smoking norms were endorsed, with just 16% of adults (12% of smokers) believing smoking was uncommon. Injunctive non-smoking norms were more prevalent, with 60–77% of adults (17–48% of smokers) viewing smoking as something of which others disapproved. Personal non-smoking norms were also prevalent among all adults (73% indicated they would prefer to live with a non-smoker) but not smokers (69% had no preference). Smokers who endorsed stronger descriptive non-smoking norms had increased odds of reporting high motivation to stop smoking (ORadj = 1.63, 95%CI 1.06–2.52). Female (but not male) past-year smokers who endorsed stronger injunctive (ORadj = 2.19, 95%CI 1.41–3.42) and personal (ORadj = 1.90, 95%CI 1.29–2.82) non-smoking norms had increased odds of having made a past-year quit attempt. In conclusion, perceived descriptive non-smoking norms are not held by the majority of adults in England. Injunctive and personal non-smoking norms are prevalent among all adults but lower among smokers. There is some evidence that smokers – in particular, women – who endorse stronger non-smoking norms are more likely to be motivated to stop smoking and to make a quit attempt

Principles of systems engineering management: Reflections from 45 years of spacecraft technology research and development at the mullard space science laboratory

Based on 45 years of experience conducting research and development into spacecraft instrumentation and 13 years' experience teaching Systems Engineering in a range of industries, the Mullard Space Science Laboratory at University College London (UCL) has identified a set of guiding principles that have been invaluable in delivering successful projects in the most demanding of environments. The five principles are: 'principles govern process', 'seek alternative systems perspectives', 'understand the enterprise context', 'integrate systems engineering and project management', and 'invest in the early stages of projects'. A common thread behind the principles is a desire to foster the ability to anticipate and respond to a changing environment with a constant focus on achieving long-term value for the enterprise. These principles are applied in space projects and have been spun-out to non-space projects (primarily through UCL's Centre for Systems Engineering). They are also embedded in UCL's extensive teaching and professional training programme. © 2012 by Author Name

A bird's eye view of discard reforms: bird-borne cameras reveal seabird/fishery interactions.

notes: PMCID: PMC3590202types: Journal Article; Research Support, Non-U.S. Gov'tCopyright: © 2013 Votier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Commercial capture fisheries produce huge quantities of offal, as well as undersized and unwanted catch in the form of discards. Declines in global catches and legislation to ban discarding will significantly reduce discards, but this subsidy supports a large scavenger community. Understanding the potential impact of declining discards for scavengers should feature in an eco-system based approach to fisheries management, but requires greater knowledge of scavenger/fishery interactions. Here we use bird-borne cameras, in tandem with GPS loggers, to provide a unique view of seabird/fishery interactions. 20,643 digital images (one min(-1)) from ten bird-borne cameras deployed on central place northern gannets Morus bassanus revealed that all birds photographed fishing vessels. These were large (>15 m) boats, with no small-scale vessels. Virtually all vessels were trawlers, and gannets were almost always accompanied by other scavenging birds. All individuals exhibited an Area-Restricted Search (ARS) during foraging, but only 42% of ARS were associated with fishing vessels, indicating much 'natural' foraging. The proportion of ARS behaviours associated with fishing boats were higher for males (81%) than females (30%), although the reasons for this are currently unclear. Our study illustrates that fisheries form a very important component of the prey-landscape for foraging gannets and that a discard ban, such as that proposed under reforms of the EU Common Fisheries Policy, may have a significant impact on gannet behaviour, particularly males. However, a continued reliance on 'natural' foraging suggests the ability to switch away from scavenging, but only if there is sufficient food to meet their needs in the absence of a discard subsidy.EU INTERREG project CHARM-IIINatural Environment Research CouncilAssociation for the Study of Animal Behaviour research gran

Multiple targets for flecainide action: implications for cardiac arrhythmogenesis

Flecainide suppresses cardiac tachyarrhythmias including paroxysmal atrial fibrillation, supraventricular tachycardia and arrhythmic long QT syndromes (LQTS), as well as the Ca(2+) -mediated, catecholaminergic polymorphic ventricular tachycardia (CPVT). However, flecainide can also exert pro-arrhythmic effects most notably following myocardial infarction and when used to diagnose Brugada syndrome (BrS). These divergent actions result from its physiological and pharmacological actions at multiple, interacting levels of cellular organization. These were studied in murine genetic models with modified Nav channel or intracellular ryanodine receptor (RyR2)-Ca(2+) channel function. Flecainide accesses its transmembrane Nav 1.5 channel binding site during activated, open, states producing a use-dependent antagonism. Closing either activation or inactivation gates traps flecainide within the pore. An early peak INa related to activation of Nav channels followed by rapid de-activation, drives action potential (AP) upstrokes and their propagation. This is diminished in pro-arrhythmic conditions reflecting loss of function of Nav 1.5 channels, such as BrS, accordingly exacerbated by flecainide challenge. Contrastingly, pro-arrhythmic effects attributed to prolonged AP recovery by abnormal late INaL following gain-of-function modifications of Nav 1.5 channels in LQTS3 are reduced by flecainide. Anti-arrhythmic effects of flecainide that reduce triggering in CPVT models mediated by sarcoplasmic reticular Ca(2+) release could arise from its primary actions on Nav channels indirectly decreasing [Ca(2+) ]i through a reduced [Na(+) ]i and/or direct open-state RyR2-Ca(2+) channel antagonism. The consequent [Ca(2+) ]i alterations could also modify AP propagation velocity and therefore arrhythmic substrate through its actions on Nav 1.5 channel function. This is consistent with the paradoxical differences between flecainide actions upon Na(+) currents, AP conduction and arrhythmogenesis under circumstances of normal and increased RyR2 function.S.C.S. and A.P.J. are funded by the British Heart Foundation (PG/14/79/31102). K.J. is funded by the Fundamental Research Grant Scheme (FRGS/2/2014/SKK01/PERDANA/ 02/1), Ministry of Education, Malaysia and the Research Support Fund, Faculty of Health and Medical Science, University of Surrey. A.F.D. is funded by the National Health and Medical Research Council (NHMRC) of Australia (APP1126201). A.J.T. is funded by the British Heart Foundation (PG/13/39/3029). C.L.H.H. is funded by the Medical Research Council (MR/M001288/1), Wellcome Trust (105727/Z/14/Z), British Heart Foundation (PG/14/79/ 31102), the McVeigh Benefaction and SADS UK

Jury Systems Around the World

Lay citizens participate as decision makers in the legal systems of many countries. This review describes the different approaches that countries employ to integrate lay decision makers, contrasting in particular the use of juries composed of all citizens with mixed decision-making bodies of lay and law-trained judges. The review discusses research on the benefits and drawbacks of lay legal decision making as well as international support for the use of ordinary citizens as legal decision makers, with an eye to explaining a recent increase in new jury systems around the world. The review calls for more comparative work on diverse approaches to lay participation, examining how different methods of including lay participation promote or detract from fact finding, legal consciousness, civic engagement, and citizen power