Influence of shear-thinning blood rheology on the laminar-turbulent transition over a backward facing step

Cardiovascular diseases are the leading cause of death globally and there is an unmet need for effective, safer blood-contacting devices, including valves, stents and artificial hearts. In these, recirculation regions promote thrombosis, triggering mechanical failure, neurological dysfunction and infarctions. Transitional flow over a backward facing step is an idealised model of these flow conditions; the aim was to understand the impact of non-Newtonian blood rheology on modelling this flow. Flow simulations of shear-thinning and Newtonian fluids were compared for Reynolds numbers ( R e ) covering the comprehensive range of laminar, transitional and turbulent flow for the first time. Both unsteady Reynolds Averaged Navier–Stokes ( k − ω SST) and Smagorinsky Large Eddy Simulations (LES) were assessed; only LES correctly predicted trends in the recirculation zone length for all R e . Turbulent-transition was assessed by several criteria, revealing a complex picture. Instantaneous turbulent parameters, such as velocity, indicated delayed transition: R e = 1600 versus R e = 2000, for Newtonian and shear-thinning transitions, respectively. Conversely, when using a Re defined on spatially averaged viscosity, the shear-thinning model transitioned below the Newtonian. However, recirculation zone length, a mean flow parameter, did not indicate any difference in the transitional Re between the two. This work shows a shear-thinning rheology can explain the delayed transition for whole blood seen in published experimental data, but this delay is not the full story. The results show that, to accurately model transitional blood flow, and so enable the design of advanced cardiovascular devices, it is essential to incorporate the shear-thinning rheology, and to explicitly model the turbulent eddies

Original Article

The present paper deals with an investigation on the changes appearing in the mucous membrane of the nose (physiologic atrophy) in normal persons of different age groups, as contrasted with a wasting of the mucous mambrane of the nose in cases of atrophic rhinitis. The investigation has been performed for the purpose of contributing to the studies of the pathology of atrophic rhinitis. 1. Pathologic changes of a considerable degree were. observed in the epithelium in quite a large section of infants and children where it had been considered normal as a results of macroscopic examinations. 2. Metaplasia of the epithelial cells developing in the mucous membrane in the forepart of the respiratory region seems to occur as a result of the stimulus applied from without. The phenomenon was marked in the front and along the lower edge of the inferior turbinal, showing a tendency to increase in magnitude as the age advance. It did not, however, spread over a wide area, nor was there any marked development of cornification. An increase in mucus secretion, as well as in the number of goblet cells, was noticed in the epithelium as the age advance. Mucous degeneration gradually set in at the end of forties, becoming marked in the sixties. 4. In the basal membrane, the hyaline layer, which is its secondary form, grew in size with age, and a substance which stains with Hale\u27s stain was detected in it. This substance seems to have an important share in the mucus secreting function of the epithelium. 5. It seems that the epithelium of the mucous membrane of the upper respiratory tract continues to function even in considerably advanced ages. 6. The lymphoid tissue situated underneath the epithelium attained the largest quantity in persons about 20 years old; it began to diminish and grow less thick in persons over 40. The presence of the elastic fiber was noticed in the subepithelial layer in all age groups, though the number of persons with this phenomenon was small.7. The glands wers under-developed in children of about 10; they grew rapidly after that age until about 40 when they began to show a tendency to atrophy. 8. It seems that the periglandular lymphocytes, which infiltrate without bringing about the disintegration of the glands, take charge of the metabolism of the glands. A large number of them were found in infancy but they showed a marked decrease in number in persons over about 40. It would seem that, in highly advanced ages, non-inflammatory disintegration of the glands could possibly occur as a result of the infiltration of the lymphoid tissue. 9. The formation of the oncocyte, an unusual cell of the epithelium of the gland which characterizes the old age, was noticed in 7 cases. 10. The blood vessels manifested changes of a high degree in persons of advanced ages: they revealed evidences of functional disturbance of a high degree when stained by the stains of H. E, Weigert, PAS and Hale. This would show the measure of the influence that has been exerted on the function of the mucous membrane. 11. Corpora cavernosa was under-developed in infancy but became well-developed in persons of about 20; a decrease in the number of bodies and a diminution in size of the inner lumen became marked in persons over 40, becoming more marked in persons over 50

Accounting for Equity Considerations in Cost-Effectiveness Analysis : A Systematic Review of Rotavirus Vaccine in Low- and Middle-Income Countries

Additional file 3: Appendix C. Full data table of results

Inducible Costimulator Expression Regulates the Magnitude of Th2-Mediated Airway Inflammation by Regulating the Number of Th2 Cells

Inducible Costimulator (ICOS) is an important regulator of Th2 lymphocyte function and a potential immunotherapeutic target for allergy and asthma. A SNP in the ICOS 5' promoter in humans is associated with increased atopy and serum IgE in a founder population and increased ICOS surface expression and Th2 cytokine production from peripheral blood mononuclear cells. However, it is unknown if increased ICOS expression contributes to disease progression or is a result of disease pathology.We developed a mouse model in which ICOS surface expression levels are genetically predetermined to test our hypothesis that genetic regulation of ICOS expression controls the severity of Th2 responses in vivo. Using ICOS+/+ and ICOS+/- mice in a Th2 model of airway inflammation, we found that T cells from the ICOS+/- mice had reduced ICOS expression and decreased Th2-mediated inflammation in vivo. Although the activation status of the T cells did not differ, T cells isolated from the lungs and draining lymph nodes of ICOS+/- mice at the peak of inflammation produced less Th2 cytokines upon stimulation ex vivo. Using 4get mice, which express GFP upon IL-4 transcription, we determined that the decreased Th2 cytokines in ICOS+/- is due to reduced percentage of Th2 cells and not a defect in their ability to produce IL-4.These data suggest that in both mice and humans, the level of ICOS surface expression regulates the magnitude of the in vivo Th2 response, perhaps by influencing Th2 differentiation

Crop Updates 2007 - Farming Systems

This session covers forty papers from different authors: 1. Quality Assurance and industry stewardship, David Jeffries, Better Farm IQ Manager, Cooperative Bulk Handling 2. Sothis: Trifolium dasyurum (Eastern Star clover), A. Loi, B.J. Nutt and C.K. Revell, Department of Agriculture and Food 3. Poor performing patches of the paddock – to ameliorate or live with low yield? Yvette Oliver1, Michael Robertson1, Bill Bowden2, Kit Leake3and Ashley Bonser3, CSIRO Sustainable Ecosystems1, Department of Food and Agriculture2, Kellerberrin Farmer3 4. What evidence is there that PA can pay? Michael Robertson, CSIRO Floreat, Ian Maling, SilverFox Solutions and Bindi Isbister, Department of Agriculture and Food 5.The journey is great, but does PA pay? Garren Knell, ConsultAg; Alison Slade, Department of Agriculture and Food, CFIG 6. 2007 Seasonal outlook, David Stephens and Michael Meuleners, Department of Agriculture and Food 7. Towards building farmer capacity to better manage climate risk, David Beard and Nicolyn Short, Department of Agriculture and Food 8. A NAR farmers view of his farming system in 2015, Rob Grima, Department of Agriculture and Food 9. Biofuels opportunities in Australia, Ingrid Richardson, Food and Agribusiness Research, Rabobank 10. The groundwater depth on the hydrological benefits of lucerne and the subsequent recharge values, Ruhi Ferdowsian1and Geoff Bee2; 1Department of Agriculture and Food, 2Landholder, Laurinya, Jerramungup 11. Subsoil constraints to crop production in the high rainfall zone of Western Australia, Daniel Evans1, Bob Gilkes1, Senthold Asseng2and Jim Dixon3; 1University of Western Australia, 2CSIRO Plant Industry, 3Department of Agriculture and Food 12. Prospects for lucerne in the WA wheatbelt, Michael Robertson, CSIRO Floreat, Felicity Byrne and Mike Ewing, CRC for Plant-Based Management of Dryland Salinity, Dennis van Gool, Department of Agriculture and Food 13. Nitrous oxide emissions from a cropped soil in the Western Australian grainbelt, Louise Barton1, Ralf Kiese2, David Gatter3, Klaus Butterbach-Bahl2, Renee Buck1, Christoph Hinz1and Daniel Murphy1,1School of Earth and Geographical Sciences, The University of Western Australia, 2Institute for Meteorology and Climate Research, Atmospheric Environmental Research, Garmisch-Partenkirchen, Germany, 3The Department of Agriculture and Food 14. Managing seasonal risk is an important part of farm management but is highly complex and therefore needs a ‘horses for courses’ approach, Cameron Weeks, Planfarm / Mingenew-Irwin Group, Dr Michael Robertson, Dr Yvette Oliver, CSIRO Sustainable Ecosystems and Dr Meredith Fairbanks, Department of Agriculture and Food 15. Novel use application of clopyralid in lupins, John Peirce, and Brad Rayner Department of Agriculture and Food 16. Long season wheat on the South Coast – Feed and grain in a dry year – a 2006 case study, Sandy White, Department of Agriculture and Food 17. Wheat yield response to potassium and the residual value of PKS fertiliser drilled at different depths, Paul Damon1, Bill Bowden2, Qifu Ma1 and Zed Rengel1; Faculty of Natural and Agricultural Sciences, The University of Western Australia1, Department of Agriculture and Food2 18. Saltbush as a sponge for summer rain, Ed Barrett-Lennard and Meir Altman, Department of Agriculture and Food and CRC for Plant-based Management of Dryland Salinity 19. Building strong working relationships between grower groups and their industry partners, Tracey M. Gianatti, Grower Group Alliance 20. To graze or not to graze – the question of tactical grazing of cereal crops, Lindsay Bell and Michael Robertson, CSIRO Sustainable Ecosystems 21. Can legume pastures and sheep replace lupins? Ben Webb and Caroline Peek, Department of Agriculture and Food 22. EverGraze – livestock and perennial pasture performance during a drought year, Paul Sanford, Department of Agriculture and Food, and CRC for Plant-based Management of Dryland Salinity 23. Crop survival in challenging times, Paul Blackwell1, Glen Riethmuller1, Darshan Sharma1and Mike Collins21Department of Agriculture and Food, 2Okura Plantations, Kirikiri New Zealand 24. Soil health constraints to production potential – a precision guided project, Frank D’Emden, and David Hall, Department of Agriculture and Food 25. A review of pest and disease occurrence in 2006, Mangano, G.P. and Severtson, D.L., Department of Agriculture and Food 26. e-weed – an information resource on seasonal weed management issues, Vanessa Stewart and Julie Roche, Department of Agriculture and Food 27. Review of Pesticide Legislation and Policies in Western Australia, Peter Rutherford, BSc (Agric.), Pesticide Legislation Review, Office of the Chief Medical Adviser, WA Department of Health 28. Future wheat yields in the West Australian wheatbelt, Imma Farré and Ian Foster, Department of Agriculture and Food, Stephen Charles, CSIRO Land and Water 29. Organic matter in WA arable soils: What’s active and what’s not, Frances Hoyle, Department of Agriculture and Food, Australia and Daniel Murphy, UWA 30. Soil quality indicators in Western Australian farming systems, D.V. Murphy1, N. Milton1, M. Osman1, F.C. Hoyle2, L.K Abbott1, W.R. Cookson1and S. Darmawanto1; 1UWA, 2Department of Agriculture and Food 31. Impact of stubble on input efficiencies, Geoff Anderson, formerly employed by Department of Agriculture and Food 32. Mixed farming vs All crop – true profit, not just gross margins, Rob Sands and David McCarthy, FARMANCO Management Consultants, Western Australia 33. Evaluation of Local Farmer Group Network – group leaders’ surveys 2005 and 2006, Paul Carmody, Local Farmer Group Network, Network Coordinator, UWA 34. Seeding rate and nitrogen application and timing effects in wheat, J. Russell, Department of Agriculture and Food, J. Eyres, G. Fosbery and A. Roe, ConsultAg, Northam 35. Foliar fungicide application and disease control in barley, J. Russell, Department of Agriculture and Food, J. Eyres, G. Fosbery and A. Roe, ConsultAg, Northam 36. Brown manuring effects on a following wheat crop in the central wheatbelt, , J. Russell, Department of Agriculture and Food, J. Eyres, G. Fosbery and A. Roe, ConsultAg, Northam 37. Management of annual pastures in mixed farming systems – transition from a dry season, Dr Clinton Revell and Dr Phil Nichols; Department of Agriculture and Food 38. The value of new annual pastures in mixed farm businesses of the wheatbelt, Dr Clinton Revell1, Mr Andrew Bathgate2and Dr Phil Nichols1; 1Department of Agriculture and Food, 2Farming Systems Analysis Service, Albany 39. The influence of winter SOI and Indian Ocean SST on WA winter rainfall, Meredith Fairbanks and Ian Foster, Department of Agriculture and Food 40. Market outlook – Grains, Anne Wilkins, Market Analyst, Grains, Department of Agriculture and Foo

The asthma epidemic and our artificial habitats

BACKGROUND: The recent increase in childhood asthma has been a puzzling one. Recent views focus on the role of infection in the education of the immune system of young children. However, this so called hygiene hypothesis fails to answer some important questions about the current trends in asthma or to account for environmental influences that bear little relation to infection. DISCUSSION: The multi-factorial nature of asthma, reflecting the different ways we tend to interact with our environment, mandates that we look at the asthma epidemic from a broader perspective. Seemingly modern affluent lifestyles are placing us increasingly in static, artificial, microenvironments very different from the conditions prevailed for most part of our evolution and shaped our organisms. Changes that occurred during the second half of the 20th century in industrialized nations with the spread of central heating/conditioning, building insulation, hygiene, TV/PC/games, manufactured food, indoor entertainment, cars, medical care, and sedentary lifestyles all seem to be depriving our children from the essential inputs needed to develop normal airway function (resistance). Asthma according to this view is a manifestation of our respiratory maladaptation to modern lifestyles, or in other words to our increasingly artificial habitats. The basis of the artificial habitat notion may lie in reduced exposure of innate immunity to a variety of environmental stimuli, infectious and non-infectious, leading to reduced formulation of regulatory cells/cytokines as well as inscribed regulatory pathways. This could contribute to a faulty checking mechanism of non-functional Th2 (and likely Th1) responses, resulting in asthma and other immuno-dysregulation disorders. SUMMARY: In this piece I discuss the artificial habitat concept, its correspondence with epidemiological data of asthma and allergy, and provide possible immunological underpinning for it from an evolutionary perspective of health and disease

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation