Resolution requirements for numerical simulations of transition

The resolution requirements for direct numerical simulations of transition to turbulence are investigated. A reliable resolution criterion is determined from the results of several detailed simulations of channel and boundary-layer transition

Primary versus Staged Closure of Exomphalos Major: Cardiac Anomalies Do Not Affect Outcome

Aim: The objective of the study is to describe management of exomphalos major and investigate the effect of congenital cardiac anomalies. / Methods: A single-center retrospective review (with audit approval) was performed of neonates with exomphalos major (fascial defect ≥ 5cm ± liver herniation) between 2004 and 2014. Demographic and operative data were collected and outcomes compared between infants who had primary or staged closure. Data, median (range), were analyzed appropriately. Results: A total of 22 patients were included, 20 with liver herniation and 1 with pentalogy of Cantrell. Gestational age was 38 (30–40) weeks, birth weight 2.7 (1.4–4.6) kg, and 13 (60%) were male. Two were managed conservatively due to severe comorbidities, 5 underwent primary closure, and 15 had application of Prolene (Ethicon Inc) mesh silo and serial reduction. Five died, including two managed conservatively, none primarily of the exomphalos. Survivors were followed up for 38 months (2–71). Cardiac anomalies were present in 20 (91%) patients: 8 had minor and 12 major anomalies. Twelve (55%) patients had other anomalies. Primary closure was associated with shorter length of stay (13 vs. 85 days, p = 0.02), but infants had similar lengths of intensive care stay, duration of parenteral feeds, and time to full feeds. Infants with cardiac anomalies had shorter times to full closure (28 vs. 62 days, p = 0.03), but other outcomes were similar. / Conclusion: Infants whose defect can be closed primarily have a shorter length of stay, but other outcomes are similar. Infants with more significant abdominovisceral disproportion are managed with staged closure; the presence of major cardiac anomalies does not affect surgical outcome

Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

An overview of using small punch testing for mechanical characterization of MCrAlY bond coats

Considerable work has been carried out on overlay bond coats in the past several decades because of its excellent oxidation resistance and good adhesion between the top coat and superalloy substrate in the thermal barrier coating systems. Previous studies mainly focus on oxidation and diffusion behavior of these coatings. However, the mechanical behavior and the dominant fracture and deformation mechanisms of the overlay bond coats at different temperatures are still under investigation. Direct comparison between individual studies has not yet been achieved due to the fragmentary data on deposition processes, microstructure and, more apparently, the difficulty in accurately measuring the mechanical properties of thin coatings. One of the miniaturized specimen testing methods, small punch testing, appears to have the potential to provide such mechanical property measurements for thin coatings. The purpose of this paper is to give an overview of using small punch testing to evaluate material properties and to summarize the available mechanical properties that include the ductile-to-brittle transition and creep of MCrAlY bond coat alloys, in an attempt to understand the mechanical behavior of MCrAlY coatings over a broad temperature range

Mechanisms of decadal variability in the Labrador Sea and the wider North Atlantic in a high-resolution climate model

A necessary step before assessing the performance of decadal predictions is the evaluation of the processes that bring memory to the climate system, both in climate models and observations. These mechanisms are particularly relevant in the North Atlantic, where the ocean circulation, related to both the Subpolar Gyre and the Meridional Overturning Circulation (AMOC), is thought to be important for driving significant heat content anomalies. Recently, a rapid decline in observed densities in the deep Labrador Sea has pointed to an ongoing slowdown of the AMOC strength taking place since the mid 90s, a decline also hinted by in-situ observations from the RAPID array. This study explores the use of Labrador Sea densities as a precursor of the ocean circulation changes, by analysing a 300-year long simulation with the state-of-the-art coupled model HadGEM3-GC2. The major drivers of Labrador Sea density variability are investigated, and are characterised by three major contributions. First, the integrated effect of local surface heat fluxes, mainly driven by year-to-year changes in the North Atlantic Oscillation, which accounts for 62% of the total variance. Additionally, two multidecadal-to-centennial contributions from the Greenland-Scotland Ridge outflows are quantified; the first associated with freshwater exports via the East Greenland Current, and the second with density changes in the Denmark Strait Overflow. Finally, evidence is shown that decadal trends in Labrador Sea densities are followed by important atmospheric impacts. In particular, a negative winter NAO response appears to follow the positive Labrador Sea density trends, and provides a phase reversal mechanism

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Anxiety and Depression in Adults with Autism Spectrum Disorder: A Systematic Review and Meta-analysis

Adults with autism spectrum disorder (ASD) are thought to be at disproportionate risk of developing mental health comorbidities, with anxiety and depression being considered most prominent amongst these. Yet, no systematic review has been carried out to date to examine rates of both anxiety and depression focusing specifically on adults with ASD. This systematic review and meta-analysis examined the rates of anxiety and depression in adults with ASD and the impact of factors such as assessment methods and presence of comorbid intellectual disability (ID) diagnosis on estimated prevalence rates. Electronic database searches for studies published between January 2000 and September 2017 identified a total of 35 studies, including 30 studies measuring anxiety (n = 26 070; mean age = 30.9, s.d. = 6.2 years) and 29 studies measuring depression (n = 26 117; mean age = 31.1, s.d. = 6.8 years). The pooled estimation of current and lifetime prevalence for adults with ASD were 27% and 42% for any anxiety disorder, and 23% and 37% for depressive disorder. Further analyses revealed that the use of questionnaire measures and the presence of ID may significantly influence estimates of prevalence. The current literature suffers from a high degree of heterogeneity in study method and an overreliance on clinical samples. These results highlight the importance of community-based studies and the identification and inclusion of well-characterized samples to reduce heterogeneity and bias in estimates of prevalence for comorbidity in adults with ASD and other populations with complex psychiatric presentations

Clostridium difficile infection.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota

A framework for generalized subspace pattern mining in high-dimensional datasets

Background A generalized notion of biclustering involves the identification of patterns across subspaces within a data matrix. This approach is particularly well-suited to analysis of heterogeneous molecular biology datasets, such as those collected from populations of cancer patients. Different definitions of biclusters will offer different opportunities to discover information from datasets, making it pertinent to tailor the desired patterns to the intended application. This paper introduces ‘GABi’, a customizable framework for subspace pattern mining suited to large heterogeneous datasets. Most existing biclustering algorithms discover biclusters of only a few distinct structures. However, by enabling definition of arbitrary bicluster models, the GABi framework enables the application of biclustering to tasks for which no existing algorithm could be used. Results First, a series of artificial datasets were constructed to represent three clearly distinct scenarios for applying biclustering. With a bicluster model created for each distinct scenario, GABi is shown to recover the correct solutions more effectively than a panel of alternative approaches, where the bicluster model may not reflect the structure of the desired solution. Secondly, the GABi framework is used to integrate clinical outcome data with an ovarian cancer DNA methylation dataset, leading to the discovery that widespread dysregulation of DNA methylation associates with poor patient prognosis, a result that has not previously been reported. This illustrates a further benefit of the flexible bicluster definition of GABi, which is that it enables incorporation of multiple sources of data, with each data source treated in a specific manner, leading to a means of intelligent integrated subspace pattern mining across multiple datasets. Conclusions The GABi framework enables discovery of biologically relevant patterns of any specified structure from large collections of genomic data. An R implementation of the GABi framework is available through CRAN (http://cran.r-project.org/web/packages/GABi/index.html)

An Amish founder variant consolidates disruption of CEP55 as a cause of hydranencephaly and renal dysplasia

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.The centrosomal protein 55 kDa (CEP55 (OMIM 610000)) plays a fundamental role in cell cycle regulation and cytokinesis. However, the precise role of CEP55 in human embryonic growth and development is yet to be fully defined. Here we identified a novel homozygous founder frameshift variant in CEP55, present at low frequency in the Amish community, in two siblings presenting with a lethal foetal disorder. The features of the condition are reminiscent of a Meckel-like syndrome comprising of Potter sequence, hydranencephaly, and cystic dysplastic kidneys. These findings, considered alongside two recent studies of single families reporting loss of function candidate variants in CEP55, confirm disruption of CEP55 function as a cause of this clinical spectrum and enable us to delineate the cardinal clinical features of this disorder, providing important new insights into early human development.Medical Research CouncilNewlife Foundation for disabled childre