What is the correct cost functional for variational data assimilation?

Variational approaches to data assimilation, and weakly constrained four dimensional variation (WC-4DVar) in particular, are important in the geosciences but also in other communities (often under different names). The cost functions and the resulting optimal trajectories may have a probabilistic interpretation, for instance by linking data assimilation with maximum aposteriori (MAP) estimation. This is possible in particular if the unknown trajectory is modelled as the solution of a stochastic differential equation (SDE), as is increasingly the case in weather forecasting and climate modelling. In this situation, the MAP estimator (or “most probable path” of the SDE) is obtained by minimising the Onsager–Machlup functional. Although this fact is well known, there seems to be some confusion in the literature, with the energy (or “least squares”) functional sometimes been claimed to yield the most probable path. The first aim of this paper is to address this confusion and show that the energy functional does not, in general, provide the most probable path. The second aim is to discuss the implications in practice. Although the mentioned results pertain to stochastic models in continuous time, they do have consequences in practice where SDE’s are approximated by discrete time schemes. It turns out that using an approximation to the SDE and calculating its most probable path does not necessarily yield a good approximation to the most probable path of the SDE proper. This suggest that even in discrete time, a version of the Onsager–Machlup functional should be used, rather than the energy functional, at least if the solution is to be interpreted as a MAP estimator

A patient with bacteraemia and possible endocarditis caused by a recently-discovered genomospecies of Capnocytophaga: Capnocytophaga genomospecies AHN8471: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Capnocytophaga </it>are a genus of bacteria that have been found to be the causative organisms in a range of infections, including serious conditions such as bacteraemia, endocarditis and meningitis. This has been especially true amongst those with serious comorbidities and the immunocompromised populations. Although several species are known to cause human disease, historically, laboratories have often not identified isolates to species level due to the unreliable, laborious techniques needed. With the advent of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism Analysis, identification to species level is now frequently possible and desirable, as it may provide clues as to the source of infection and its treatment.</p> <p>Case presentation</p> <p>Here we describe a case of bacteraemia and possible endocarditis in a 64-year-old white British man caused by a newly identified genomospecies of <it>Capnocytophaga </it>in a patient subsequently diagnosed with metastatic adenocarcinoma of the oesophagus. The source of the bacteraemia was presumed to be from the patient's own oral flora.</p> <p>Conclusion</p> <p>Our case further confirms the potential for <it>Capnocytophaga </it>to cause systemic infections, highlights the availability and need for identification of isolates to species level and re-emphasises the difficulty in diagnosing <it>Capnocytophaga </it>infections due to their slow growth in the laboratory.</p

Whey protein lowers systolic blood pressure and Ca-caseinate reduces serum TAG after a high-fat meal in mildly hypertensive adults

Epidemiological studies show an inverse association between dairy consumption and blood pressure (BP) but there are few data on the postprandial effects of milk proteins. This study examined their effects, compared to maltodextrin, on postprandial BP and other CVD risk markers in volunteers with mild and pre-hypertension over an 8 h period. In this double-blinded, randomised, cross-over, controlled study 27 adults ingested a high-fat, isoenergetic breakfast and lunch with 28 g whey protein, 28 g Ca-caseinate or 27 g maltodextrin. Whey protein reduced systolic BP compared with Ca-caseinate (−15.2 ± 13.6 mmHg) and maltodextrin (−23.4 ± 10.5 mmHg) up to 5 h post-ingestion. There was an improvement in arterial stiffness after whey protein compared with maltodextrin (incremental Area Under the Curve- iAUC0–8h: +14.4 ± 6.2%). Despite similar glucose levels after both whey protein and Ca-caseinate, whey protein induced a higher insulin response than Cacaseinate (iAUC0–8h: +219.5 ± 54.6 pmol/L). Ca-caseinate induced less suppression of non-esterified fatty acids than whey protein (iAUC0–5h: −58.9 ± 135.5 μmol/L) and maltodextrin (iAUC0–5h: −106.9 ± 89.4 μmol/L) and induced a smaller postprandial triacylglycerol response than whey protein (iAUC0–8h: −1.68 ± 0.6 mmol/L). Milk proteins co-ingestion with high-fat meals may have the potential to maintain or improve CVD risk factors

Echo-driven V-V optimization determines clinical improvement in non responders to cardiac resynchronization treatment

Echocardiography plays an integral role in the detection of mechanical dyssynchrony in patients with congestive heart failure and in predicting beneficial response to cardiac resynchronization treatment. In patients who derive sup-optimal benefit from biventricular pacing, optimization of atrioventricular delay post cardiac resynchronization treatment has been shown to improve cardiac output. Some recent reports suggest that sequential ventricular pacing may further improve cardiac output. The mechanism whereby sequential ventricular pacing improves cardiac output is likely improved inter and possibly intraventricular synchrony, however these speculations have not been confirmed. In this report we describe the beneficial effect of sequential V-V pacing on inter and intraventricular synchrony, cardiac output and mitral regurgitation severity as the mechanisms whereby sequential biventricular pacing improves cardiac output and functional class in 8 patients who had derived no benefit or had deteriorated after CRT. Online tissue Doppler imaging including tissue velocity imaging, tissue synchronization imaging and strain and strain rate imaging were used in addition to conventional pulsed wave and color Doppler during sequential biventricular pacemaker programming

Previous Lung Diseases and Lung Cancer Risk: A Systematic Review and Meta-Analysis

In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer, a meta-analysis and systematic review was conducted.Relevant studies were identified through MEDLINE searches. Using random effects models, summary effects of specific previous conditions were evaluated separately and combined. Stratified analyses were conducted based on smoking status, gender, control sources and continent.A previous history of COPD, chronic bronchitis or emphysema conferred relative risks (RR) of 2.22 (95% confidence interval (CI): 1.66, 2.97) (from 16 studies), 1.52 (95% CI: 1.25, 1.84) (from 23 studies) and 2.04 (95% CI: 1.72, 2.41) (from 20 studies), respectively, and for all these diseases combined 1.80 (95% CI: 1.60, 2.11) (from 39 studies). The RR of lung cancer for subjects with a previous history of pneumonia was 1.43 (95% CI: 1.22-1.68) (from 22 studies) and for subjects with a previous history of tuberculosis was 1.76 (95% CI=1.49, 2.08), (from 30 studies). Effects were attenuated when restricting analysis to never smokers only for COPD/emphysema/chronic bronchitis (RR=1.22, 0.97-1.53), however remained significant for pneumonia 1.36 (95% CI: 1.10, 1.69) (from 8 studies) and tuberculosis 1.90 (95% CI: 1.45, 2.50) (from 11 studies).Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer

Streamwise-travelling viscous waves in channel flows

The unsteady viscous flow induced by streamwise-travelling waves of spanwise wall velocity in an incompressible laminar channel flow is investigated. Wall waves belonging to this category have found important practical applications, such as microfluidic flow manipulation via electro-osmosis and surface acoustic forcing and reduction of wall friction in turbulent wall-bounded flows. An analytical solution composed of the classical streamwise Poiseuille flow and a spanwise velocity profile described by the parabolic cylinder function is found. The solution depends on the bulk Reynolds number R, the scaled streamwise wavelength (Formula presented.), and the scaled wave phase speed U. Numerical solutions are discussed for various combinations of these parameters. The flow is studied by the boundary-layer theory, thereby revealing the dominant physical balances and quantifying the thickness of the near-wall spanwise flow. The Wentzel–Kramers–Brillouin–Jeffreys (WKBJ) theory is also employed to obtain an analytical solution, which is valid across the whole channel. For positive wave speeds which are smaller than or equal to the maximum streamwise velocity, a turning-point behaviour emerges through the WKBJ analysis. Between the wall and the turning point, the wall-normal viscous effects are balanced solely by the convection driven by the wall forcing, while between the turning point and the centreline, the Poiseuille convection balances the wall-normal diffusion. At the turning point, the Poiseuille convection and the convection from the wall forcing cancel each other out, which leads to a constant viscous stress and to the break down of the WKBJ solution. This flow regime is analysed through a WKBJ composite expansion and the Langer method. The Langer solution is simpler and more accurate than the WKBJ composite solution, while the latter quantifies the thickness of the turning-point region. We also discuss how these waves can be generated via surface acoustic forcing and electro-osmosis and propose their use as microfluidic flow mixing devices. For the electro-osmosis case, the Helmholtz–Smoluchowski velocity at the edge of the Debye–Hückel layer, which drives the bulk electrically neutral flow, is obtained by matched asymptotic expansion

Suicidal thoughts and depressive feelings amongst Estonian schoolchildren: effect of family relationship and family structure

Depressive feelings and suicidal ideation in a non-clinical sample of adolescents in Estonia were analysed in the context of family structure, mutual relationships amongst family members and schoolchildren's preferences regarding intimate personal contacts with particular family members. Data from the WHO collaborative study 'Health Behaviour in School-aged Children 2005/2006' (HBSC) were used. A representative sample of schoolchildren aged 11, 13 and 15 years completed the semi-structured questionnaire. The analyses included only adolescents living in households with at least one birth parent. The subjects were 4,389 schoolchildren (2,178 boys and 2,211 girls), who were divided into three groups based on: (1) suicidal thoughts, with or without depressive feelings; (2) depressive feelings; and (3) neither suicidal thoughts nor depressive feelings. Multinomial logistic regression was used. The proportion of depressive feelings increased with age for both boys and girls. Girls expressed depressive feelings more frequently than boys from ages 13 and 15 years, and suicidal thoughts from age 15 years. Self-reported satisfaction with relationships in the family reduced the likelihood of depressive feelings and suicidal thoughts. Good communication with the parents reduced the likelihood of suicidal thoughts in all age groups. Adolescents who were satisfied with their family relationships suffered less frequently from depressive feelings and suicidal thoughts. The best environment for an adolescent was a family with both birth parents. Of the adolescents in 'non-intact' families, those with a step-parent in the family showed suicidal thoughts more frequently than those in single-parent families. Associations between family-related variables and suicidal thoughts were significant even after adjusting for family economic deprivation score

Genetic Loci Involved in Antibody Response to Mycobacterium avium ssp. paratuberculosis in Cattle

Background: Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic enteritis in a wide range of animal species. In cattle, MAP causes a chronic disease called Johne's disease, or paratuberculosis, that is not treatable and the efficacy of vaccine control is controversial. The clinical phase of the disease is characterised by diarrhoea, weight loss, drop in milk production and eventually death. Susceptibility to MAP infection is heritable with heritability estimates ranging from 0.06 to 0.10. There have been several studies over the last few years that have identified genetic loci putatively associated with MAP susceptibility, however, with the availability of genome-wide high density SNP maker panels it is now possible to carry out association studies that have higher precision. Methodology/Principal Findings: The objective of the current study was to localize genes having an impact on Johne's disease susceptibility using the latest bovine genome information and a high density SNP panel (Illumina BovineSNP50 BeadChip) to perform a case/control, genome-wide association analysis. Samples from MAP case and negative controls were selected from field samples collected in 2007 and 2008 in the province of Lombardy, Italy. Cases were defined as animals serologically positive for MAP by ELISA. In total 966 samples were genotyped: 483 MAP ELISA positive and 483 ELISA negative. Samples were selected randomly among those collected from 119 farms which had at least one positive animal. Conclusion/Significance: The analysis of the genotype data identified several chromosomal regions associated with disease status: a region on chromosome 12 with high significance (P<5 710-6), while regions on chromosome 9, 11, and 12 had moderate significance (P<5 710-5). These results provide evidence for genetic loci involved in the humoral response to MAP. Knowledge of genetic variations related to susceptibility will facilitate the incorporation of this information into breeding programmes for the improvement of health status

Regulation of Septin Dynamics by the Saccharomyces cerevisiae Lysine Acetyltransferase NuA4

In the budding yeast Saccharomyces cerevisiae, the lysine acetyltransferase NuA4 has been linked to a host of cellular processes through the acetylation of histone and non-histone targets. To discover proteins regulated by NuA4-dependent acetylation, we performed genome-wide synthetic dosage lethal screens to identify genes whose overexpression is toxic to non-essential NuA4 deletion mutants. The resulting genetic network identified a novel link between NuA4 and septin proteins, a group of highly conserved GTP-binding proteins that function in cytokinesis. We show that acetyltransferase-deficient NuA4 mutants have defects in septin collar formation resulting in the development of elongated buds through the Swe1-dependent morphogenesis checkpoint. We have discovered multiple sites of acetylation on four of the five yeast mitotic septins, Cdc3, Cdc10, Cdc12 and Shs1, and determined that NuA4 can acetylate three of the four in vitro. In vivo we find that acetylation levels of both Shs1 and Cdc10 are reduced in a catalytically inactive esa1 mutant. Finally, we determine that cells expressing a Shs1 protein with decreased acetylation in vivo have defects in septin localization that are similar to those observed in NuA4 mutants. These findings provide the first evidence that yeast septin proteins are acetylated and that NuA4 impacts septin dynamics