Optimal ex vivo expansion of neutrophils from PBSC CD34+ cells by a combination of SCF, Flt3-L and G-CSF and its inhibition by further addition of TPO

<p>Abstract</p> <p>Background</p> <p>Autologous mobilised peripheral blood stem cell (PBSC) transplantation is now a standard approach in the treatment of haematological diseases to reconstitute haematopoiesis following myeloablative chemotherapy. However, there remains a period of severe neutropenia and thrombocytopenia before haematopoietic reconstitution is achieved. <it>Ex vivo </it>expanded PBSC have been employed as an adjunct to unmanipulated HSC transplantation, but have tended to be produced using complex cytokine mixtures aimed at multilineage (neutrophil and megakaryocyte) progenitor expansion. These have been reported to reduce or abrogate neutropenia but have little major effect on thrombocytopenia. Selective megakaryocyte expansion has been to date ineffective in reducing thrombocytopenia. This study was implemented to evaluate neutrophil specific rather than multilineage <it>ex vivo </it>expansion of PBSC for specifically focusing on reduction or abrogation of neutropenia.</p> <p>Methods</p> <p>CD34⁺cells (PBSC) were enriched from peripheral blood mononuclear cells following G-CSF-mobilisation and cultured with different permutations of cytokines to determine optimal cytokine combinations and doses for expansion and functional differentiation and maturation of neutrophils and their progenitors. Results were assessed by cell number, morphology, phenotype and function.</p> <p>Results</p> <p>A simple cytokine combination, SCF + Flt3-L + G-CSF, synergised to optimally expand and mature neutrophil progenitors assessed by cell number, phenotype, morphology and function (superoxide respiratory burst measured by chemiluminescence). G-CSF appears mandatory for functional maturation. Addition of other commonly employed cytokines, IL-3 and IL-6, had no demonstrable additive effect on numbers or function compared to this optimal combination. Addition of TPO, commonly included in multilineage progenitor expansion for development of megakaryocytes, reduced the maturation of neutrophil progenitors as assessed by number, morphology and function (respiratory burst activity).</p> <p>Conclusion</p> <p>Given that platelet transfusion support is available for autologous PBSC transplantation but granulocyte transfusion is generally lacking, and that multilineage expanded PBSC do not reduce thrombocytopenia, we suggest that instead of multilineage expansion selective neutrophil expansion based on this relatively simple cytokine combination might be prioritized for development for clinical use as an adjunct to unmanipulated PBSC transplantation to reduce or abrogate post-transplant neutropenia.</p

Absence of a relationship between immunophenotypic and colony enumeration analysis of endothelial progenitor cells in clinical haematopoietic cell sources

<p>Abstract</p> <p>Background</p> <p>The discovery of adult endothelial progenitor cells (EPC) offers potential for vascular regenerative therapies. The expression of CD34 and VEGFR2 by EPC indicates a close relationship with haematopoietic progenitor cells (HPC), and HPC-rich sources have been used to treat cardiac and limb ischaemias with apparent clinical benefit. However, the laboratory characterisation of the vasculogenic capability of potential or actual therapeutic cell autograft sources is uncertain since the description of EPC remains elusive. Various definitions of EPC based on phenotype and more recently on colony formation (CFU-EPC) have been proposed.</p> <p>Methods</p> <p>We determined EPC as defined by proposed phenotype definitions (flow cytometry) and by CFU-EPC in HPC-rich sources: bone marrow (BM); cord blood (CB); and G-CSF-mobilised peripheral blood (mPB), and in HPC-poor normal peripheral blood (nPB).</p> <p>Results</p> <p>As expected, the highest numbers of cells expressing the HPC markers CD34 or CD133 were found in mPB and least in nPB. The proportions of CD34⁺cells co-expressing CD133 is of the order mPB>CB>BM≈nPB. CD34⁺cells co-expressing VEGFR2 were also most frequent in mPB. In contrast, CFU-EPC were virtually absent in mPB and were most readily detected in nPB, the source lowest in HPC.</p> <p>Conclusion</p> <p>HPC sources differ in their content of putative EPC. Normal peripheral blood, poor in HPC and in HPC-related phenotypically defined EPC, is the richest source of CFU-EPC, suggesting no direct relationship between the proposed EPC immunophenotypes and CFU-EPC potential. It is not apparent whether either of these EPC measurements, or any, is an appropriate indicator of the therapeutic vasculogenic potential of autologous HSC sources.</p

Transport processes of particles in dilute suspensions in turbulent water flow–phase I

Modifications to an existing experimental system have been made and have been demonstrated to provide the required resolution and variable parameterization necessary for a detailed study of dilute particle suspensions in a turbulent water flow. These modifications together with the reasons for their necessity are discussed. Linearization of non-Stokesian drag has been accomplished through the introduction of a diagonal tensor into the Stokes drag force equation. It was found that non-Stokesian effects tend to be of minor importance in the response of water borne particles.U.S. Department of the InteriorU.S. Geological SurveyOpe

Application of Atomic Dielectric Resonance Spectroscopy for the screening of blood samples from patients with clinical variant and sporadic CJD

<p>Abstract</p> <p>Background</p> <p>Sub-clinical variant Creutzfeldt-Jakob disease (vCJD) infection and reports of vCJD transmission through blood transfusion emphasise the need for blood screening assays to ensure the safety of blood and transplanted tissues. Most assays aim to detect abnormal prion protein (PrP^Sc), although achieving required sensitivity is a challenge.</p> <p>Methods</p> <p>We have used innovative Atomic Dielectric Resonance Spectroscopy (ADRS), which determines dielectric properties of materials which are established by reflectivity and penetration of radio/micro waves, to analyse blood samples from patients and controls to identify characteristic ADR signatures unique to blood from vCJD and to sCJD patients. Initial sets of blood samples from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) were screened as training samples to determine group-specific ADR characteristics, and provided a basis for classification of blinded sets of samples.</p> <p>Results</p> <p>Blood sample groups from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) screened by ADRS were classified with 100% specificity and sensitivity, discriminating these by a co-variance expert analysis system.</p> <p>Conclusion</p> <p>ADRS appears capable of recognising and discriminating serum samples from vCJD, sCJD, non-CJD neurological diseases, and normal healthy adults, and might be developed to provide a system for primary screening or confirmatory assay complementary to other screening systems.</p

Reconceptualising risk: Perceptions of risk in rural and remote maternity service planning.

OBJECTIVE: to explore perceptions and examples of risk related to pregnancy and childbirth in rural and remote Australia and how these influence the planning of maternity services. DESIGN: data collection in this qualitative component of a mixed methods study included 88 semi-structured individual and group interviews (n=102), three focus groups (n=22) and one group information session (n=17). Researchers identified two categories of risk for exploration: health services risk (including clinical and corporate risks) and social risk (including cultural, emotional and financial risks). Data were aggregated and thematically analysed to identify perceptions and examples of risk related to each category. SETTING: fieldwork was conducted in four jurisdictions at nine sites in rural (n=3) and remote (n=6) Australia. PARTICIPANTS: 117 health service employees and 24 consumers. MEASUREMENTS AND FINDINGS: examples and perceptions relating to each category of risk were identified from the data. Most medical practitioners and health service managers perceived clinical risks related to rural birthing services without access to caesarean section. Consumer participants were more likely to emphasise social risks arising from a lack of local birthing services. KEY CONCLUSIONS: our analysis demonstrated that the closure of services adds social risk, which exacerbates clinical risk. Analysis also highlighted that perceptions of clinical risk are privileged over social risk in decisions about rural and remote maternity service planning. IMPLICATIONS FOR PRACTICE: a comprehensive analysis of risk that identifies how social and other forms of risk contribute to adverse clinical outcomes would benefit rural and remote people and their health services. Formal risk analyses should consider the risks associated with failure to provide birthing services in rural and remote communities as well as the risks of maintaining services

Gender Differences in Russian Colour Naming

In the present study we explored Russian colour naming in a web-based psycholinguistic experiment (http://www.colournaming.com). Colour singletons representing the Munsell Color Solid (N=600 in total) were presented on a computer monitor and named using an unconstrained colour-naming method. Respondents were Russian speakers (N=713). For gender-split equal-size samples (NF=333, NM=333) we estimated and compared (i) location of centroids of 12 Russian basic colour terms (BCTs); (ii) the number of words in colour descriptors; (iii) occurrences of BCTs most frequent non-BCTs. We found a close correspondence between females’ and males’ BCT centroids. Among individual BCTs, the highest inter-gender agreement was for seryj ‘grey’ and goluboj ‘light blue’, while the lowest was for sinij ‘dark blue’ and krasnyj ‘red’. Females revealed a significantly richer repertory of distinct colour descriptors, with great variety of monolexemic non-BCTs and “fancy” colour names; in comparison, males offered relatively more BCTs or their compounds. Along with these measures, we gauged denotata of most frequent CTs, reflected by linguistic segmentation of colour space, by employing a synthetic observer trained by gender-specific responses. This psycholinguistic representation revealed females’ more refined linguistic segmentation, compared to males, with higher linguistic density predominantly along the redgreen axis of colour space

Two Earth-sized planets orbiting Kepler-20

Since the discovery of the first extrasolar giant planets around Sun-like stars, evolving observational capabilities have brought us closer to the detection of true Earth analogues. The size of an exoplanet can be determined when it periodically passes in front of (transits) its parent star, causing a decrease in starlight proportional to its radius. The smallest exoplanet hitherto discovered has a radius 1.42 times that of the Earth's radius (R Earth), and hence has 2.9 times its volume. Here we report the discovery of two planets, one Earth-sized (1.03R Earth) and the other smaller than the Earth (0.87R Earth), orbiting the star Kepler-20, which is already known to host three other, larger, transiting planets. The gravitational pull of the new planets on the parent star is too small to measure with current instrumentation. We apply a statistical method to show that the likelihood of the planetary interpretation of the transit signals is more than three orders of magnitude larger than that of the alternative hypothesis that the signals result from an eclipsing binary star. Theoretical considerations imply that these planets are rocky, with a composition of iron and silicate. The outer planet could have developed a thick water vapour atmosphere.Comment: Letter to Nature; Received 8 November; accepted 13 December 2011; Published online 20 December 201

Damaged Intestinal Epithelial Integrity Linked to Microbial Translocation in Pathogenic Simian Immunodeficiency Virus Infections

The chronic phase of HIV infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or CD4+ T cell count. Recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed tissues from SIV-infected rhesus macaques (RMs) to provide direct in situ evidence for translocation of microbial constituents from the lumen of the intestine into the lamina propria and to draining and peripheral lymph nodes and liver, accompanied by local immune responses in affected tissues. In chronically SIV-infected RMs this translocation is associated with breakdown of the integrity of the epithelial barrier of the gastrointestinal (GI) tract and apparent inability of lamina propria macrophages to effectively phagocytose translocated microbial constituents. By contrast, in the chronic phase of SIV infection in sooty mangabeys, we found no evidence of epithelial barrier breakdown, no increased microbial translocation and no pathological immune activation. Because immune activation is characteristic of the chronic phase of progressive HIV/SIV infections, these findings suggest that increased microbial translocation from the GI tract, in excess of capacity to clear the translocated microbial constituents, helps drive pathological immune activation. Novel therapeutic approaches to inhibit microbial translocation and/or attenuate chronic immune activation in HIV-infected individuals may complement treatments aimed at direct suppression of viral replication

Crop Updates 2002 - Cereals

This session covers thirty one papers from different authors: VARIETIES AND BREEDING 1. Agronomic evaluation of wheat and barley in the central wheatbelt of Western Australia, Peter Burgess1and Gary Fawell2, 1Agritech and 2Farmanco Management 2. Evaluating stress tolerance to terminal drought by Western Australian wheats, Dean Diepeveen and Dr Tim Setter, Department of Agriculture 3. Broadscale wheat variety comparisons featuring Wyalkatchem, Jeff Russell, Department of Agriculture 4. Australian crop accreditation system variety selector, Tony Seymour, Australian Crop Accreditation System 5. Future wheat varieties, Robin Wilson, Iain Barclay,Robyn McLean, Robert Loughman, Jenny Garlinge, Bill Lambe, Neil Venn and Peter Clarke, Department of Agriculture AGRONOMY 6. Beware of wheat variety interactions with row spacing and seed rate, Mohammad Amjad and Wal Anderson, Department of Agriculture 7. Yield and falling numbers of wheat varieties on the South Coast, Mohammad Amjad and Wal Anderson, Department of Agriculture 8. Maximising wheat variety performance through agronomic management, Wal Anderson, Raffaele Del Cima, James Bee, Darshan Sharma, Sheena Lyon, Melaine Kupsch, Mohammad Amjad, Pam Burgess, Veronika Reck, Brenda Shackley, Ray Tugwell, BindiWebb and Steve Penny Jr, Department of Agriculture 9. High impact of soil type and seasonal rainfall on optimum wheat seed rate , Raffaele Del Cima and Wal Anderson Department of Agriculture 10. 101 seasons in one day: Using the ‘WA Wheat’ database to predict wheat yield, James Fisher1, Bill Bowden1, Craig Scanlan1, Senthold Asseng2and Michael Robertson2 1Department of Agriculture, 2CSIRO 11. Economics of improving compact soils, M.A. Hamza1, G. McConnell2and W.K. Anderson1, 1Department of Agriculture, 2Planfarm 12. Reducing the risks in producing durum wheat in Western Australia, Md Shahajahan Miyan and Wal Anderson, Department of Agriculture 13. Taking the Why out of Wyalkatchem – the new widely adopted wheat variety, Steve Penny, Department of Agriculture 14. Influence of nutrition and environmental factors on seed vigour in wheat, Darshan Sharma, Wal Anderson and Daya Patabendige, Department of Agriculture NUTRITION 15. N and K are important for oat yield and quality, Patrick Gethin, Stephen Loss, Tim O’Dea, Ryan Guthrie and Lisa Leaver, CSBP Futurefarm 16. Effects of nitrogen and phosphorus on the grain yield and quality of noodle wheat, Tyrone Henning1, Lionel Martin1and Wal Anderson2 1Muresk Institute of Agriculture, 2Department of Agriculture 17. Assessment of a high input fertiliser regime on the yield and quality of Gairdner barley, Narelle Hill1, Simon Wallwork2and Laurence Carslake2 1Department of Agriculture, 2Wesfarmers Landmark 18. The use of Flexi-N to achieve high yielding, high protein wheat, Darren Hughes1, Lionel Martin1, Wal Anderson2and Stephen Loss3 1Muresk Institute of Agriculture, 2Department of Agriculture, 3CSBP Futurefarm 19. Are liquid phosphorus fertilisers more efficient than solid fertilisers in Western Australia?Stephen Loss, Lisa Leaver, Ryan Guthrie, Patrick Gethin and Tim O’Dea, CSBP Futurefarm 20. Oats respond to phosphorus and potassium, Glenn McDonald, Department of Agriculture PESTS AND DISEASES 21. Cereal disease diagnostics and rust monitoring, Nichole Burges and Dominie Wright, Department of Agriculture 22. Distribution and incidence of aphids and barley yellow dwarf virus in over-summering grasses in the Western Australian wheatbelt, Jenny Hawkes and Roger Jones, Centre for Legumes in Mediterranean Agriculture and Department of Agriculture 23. Spring sprays for powdery mildew control in cereals, Kith Jayasena1, Kazue Tanaka1, Vanessa Johnson1, Robert Loughman1and Josh Jury2 1Department of Agriculture, 2Wesfarmers Landmark 24. Impact of root lesion nematodes on wheat and triticale in Western Australia, Sean Kelly and Shashi Sharma, Department of Agriculture 25. Cropping options for the management of root lesion nematodes in Western Australia, Sean Kelly, Shashi Sharma and Robert Loughman, Department of Agriculture 26. Cereal rust update 2002 – new stem rust on Camm wheat, Robert Loughman1and Robert Park2 1Department of Agriculture, 2University of Sydney 27. Cereal aphids and direct feeding damage to cereals, Phil Michael, Department of Agriculture 28. A decision support system for control of aphids and BYDV in cereal crops, Debbie Thackray, Jenny Hawkes and Roger Jones, Department of Agriculture and Centre for Legumes in Mediterranean Agriculture STORAGE 29. Aeration – opportunity for profit, Christopher Newman, Department of Agriculture CLIMATE 30. Financial impact of frost on the Western Australian grains industry, Garren Knell and Kim Povey, ConsultAg 31. Summary of 2001 weather and seasonal prospects for 2002, David Stephens, Department of Agricultur

Crop Updates 2001 - Cereals

This session covers forty two papers from different authors: PLENARY 1. Planning your cropping program in season 2001, Dr Ross Kingwell, Agriculture Western Australia and University of Western Australia WORKSHOP 2. Can we produce high yields without high inputs? Wal Anderson, Centre for Cropping Systems, Agriculture Western Australia VARIETIES 3. Local and interstate wheat variety performance and $ return to WA growers, Eddy Pol, Peter Burgess and Ashley Bacon, Agritech Crop Research CROP ESTABLISHMENT 4 Soil management of waterlogged soils, D.M. Bakker, G.J. Hamilton, D. Houlbrooke and C. Spann, Agriculture Western Australia 5. Effect of soil amelioration on wheat yield in a very dry season, M.A Hamza and W.K. Anderson, Agriculture Western Australia 6. Fuzzy tramlines for more yield and less weed, Paul Blackwell1 and Maurice Black2 1Agriculture Western Australia, 2Harbour Lights Estate, Geraldton 7. Tramline farming for dollar benefits, Paul Blackwell, Agriculture Western Australia NUTRITION 8. Soil immobile nutrients for no-till crops, M.D.A. Bolland1, R.F. Brennan1,and W.L. Crabtree2, 1Agriculture Western Australia, 2Western Australian No-Tillage Farmers Association 9. Burn stubble windrows: to diagnose soil fertility problems, Bill Bowden, Chris Gazey and Ross Brennan, Agriculture Western Australia 10. Calcium: magnesium ratios; are they important? Bill Bowden1, Rochelle Strahan2, Bob Gilkes2 and Zed Rengel2 1Agriculture Western Australia, 2Department of Soil Science and Plant Nutrition, UWA 11. Responses to late foliar applications of Flexi-N, Stephen Loss, Tim O’Dea, Patrick Gethin, Ryan Guthrie, Lisa Leaver, CSBP futurefarm 12. A comparison of Flexi-N placements, Stephen Loss, Tim O’Dea, Patrick Gethin, Ryan Guthrie, Lisa Leaver, CSBP futurefarm 13. What is the best way to apply potassium? Stephen Loss, Tim O’Dea, Patrick Gethin, Ryan Guthrie, CSBP futurefarm 14. Claying affects potassium nutrition in barley, Stephen Loss, David Phelps, Tim O’Dea, Patrick Gethin, Ryan Guthrie, Lisa Leaver, CSBP futurefarm 15. Nitrogen and potassium improve oaten hay quality, Stephen Loss, Tim O’Dea, Patrick Gethin, Ryan Guthrie, Lisa Leaver, CSBP futurefarm AGRONOMY 16. Agronomic responses of new wheat varieties in the northern wheatbelt, Darshan Sharma and Wal Anderson, Agriculture Western Australia 17. Wheat agronomy research on the south coast, Mohammad Amjad and Wal Anderson, Agriculture Western Australia 18. Influence of sowing date on wheat yield and quality in the south coast environment, Mohammad Amjadand Wal Anderson, Agriculture Western Australia 19. More profit from durum, Md.Shahajahan Miyan and Wal Anderson, Agriculture Western Australia 20. Enhancing recommendations of flowering and yield in wheat, JamesFisher1, Senthold Asseng2, Bill Bowden1 and Michael Robertson3 ,1AgricultureWestern Australia, 2CSIRO Plant Industry, 3CSIRO Sustainable Ecosystems 21. When and where to grow oats, Glenn McDonald, Agriculture Western Australia 22. Managing Gaidner barley for quality, Kevin Young and Blakely Paynter, Agriculture Western Australia PESTS AND DISEASES 23. Strategies for leaf disease management in wheat, Jatinderpal Bhathal1, Cameron Weeks2, Kith Jayasena1 and Robert Loughman1 ,1Agriculture Western Australia. 2Mingenew-Irwin Group Inc 24. Strategies for leaf disease management in malting barley, K. Jayasena1, Q. Knight2 and R. Loughman1, 1Agriculture Western Australia, 2IAMA Agribusiness 25. Cereal disease diagnostics, Dominie Wright and Nichole Burges, Agriculture Western Australia 26. The big rust: Did you get your money back!! Peter Burgess, Agritech Crop Research 27. Jockey – winning the race against disease in wheat, Lisa-Jane Blacklow, Rob Hulme and Rob Giffith, Aventis CropScience 28. Distribution and incidence of aphids and barley yellow dwarf virus in over-summering grasses in WA wheatbelt, Jenny Hawkes and Roger Jones, CLIMA and Agriculture Western Australia 29. Further developments in forecasting aphid and virus risk in cereals, Debbie Thackray, Jenny Hawkes and Roger Jones, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture 30. Effect of root lesion nematodes on wheat yields in Western Australia, S. B. Sharma, S. Kelly and R. Loughman, Crop Improvement Institute, Agriculture Western Australia 31. Rotational crops and varieties for management of root lesion nematodes in Western Australia, S.B. Sharma, S. Kelly and R. Loughman, Crop Improvement Institute, Agriculture Western Australia WEEDS 32. Phenoxy herbicide tolerance of wheat, Peter Newman and Dave Nicholson, Agriculture Western Australia 33. Tolerance of wheat to phenoxy herbicides,Harmohinder S. Dhammu, Terry Piper and Mario F. D\u27Antuono, Agriculture Western Australia 34. Herbicide tolerance of durum wheats, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Agriculture Western Australia 35. Herbicide tolerance of new wheats, Harmohinder S. Dhammu, Terry Piper and David F. Nicholson, Agriculture Western Australia BREEDING 36. Towards molecular breeding of barley: construction of a molecular genetic map, Mehmet Cakir1, Nick Galwey1, David Poulsen2, Garry Ablett3, Reg Lance4, Rob Potter5 and Peter Langridge6,1Plant Sciences, Faculty of Agriculture, UWA, 2Queensland Department of Primary Industries, Qld, 3Centre for Plant Conservation Genetics Southern Cross University, Lismore NSW, 5SABC Murdoch University, WA, 6Department of Plant Science University of Adelaide, Glen Osmond SA 37. Toward molecular breeding of barley: Identifying markers linked to genes for quantitative traits, Mehmet Cakir1, Nick Galwey1, David Poulsen2, Reg Lance3, Garry Ablett4, Greg Platz2, Joe Panozzo5, Barbara Read6, David Moody5, Andy Barr7 and Peter Langridge7 , 1Plant Sciences, Faculty of Agriculture, UWA, 2Queensland Department of Primary Industries, Warwick, QLD,3Agriculture Western Australia, 4Centre for Plant Conservation Genetics, Southern Cross University, Lismore NSW, 5VIDA Private Bag 260, Horsham VIC, 6NSW Dept. of Agriculture, Wagga Wagga NSW, 7Department of Plant Science, University of Adelaide, Glen Osmond SA 38. Can we improve grain yield by breeding for greater early vigour in wheat? Tina Botwright1, Tony Condon1, Robin Wilson2 and Iain Barclay2, 1CSIRO Plant Industry, 2Agriculture Western Australia MARKETING AND QUALITY 39. The Crop Improvement Royalty, Howard Carr, Agriculture Western Australia 40. GrainGuardÔ - The development of a protection plan for the wheat industry, Greg Shea, Agriculture Western Australia CLIMATE 41. Rainfall – what happened in 2000 and the prospects for 2001, Ian Foster, Agriculture Western Australia 42. Software for climate management issues, David Tennant,Agriculture Western Australia CONTRIBUTING AUTHOR CONTACT DETAIL