Lewy Body Dementia Association\u27s Research Centers of Excellence Program: Inaugural Meeting Proceedings.

The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator\u27s meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson\u27s disease dementia (PDD), and to create a clinical trials-ready network. Four working groups (WG) were created to pursue the LBDA RCOE aims: (1) increase access to high-quality clinical care, (2) increase access to support for people living with LBD and their caregivers, (3) increase knowledge of LBD among medical and allied (or other) professionals, and (4) create infrastructure for a clinical trials-ready network as well as resources to advance the study of new therapeutics

A Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus

Lymph- and blood-borne retroviruses exploit CD169/Siglec-1-mediated capture by subcapsular sinus and marginal zone metallophilic macrophages for trans-infection of permissive lymphocytes. However, the impact of CD169-mediated virus capture on retrovirus dissemination and pathogenesis in vivo is unknown. In a murine model of the splenomegaly-inducing retrovirus Friend virus complex (FVC) infection, we find that while CD169 promoted draining lymph node infection, it limited systemic spread to the spleen. At the spleen, CD169-expressing macrophages captured incoming blood-borne retroviruses and limited their spread to the erythroblasts in the red pulp where FVC manifests its pathogenesis. CD169-mediated retroviral capture activated conventional dendritic cells 1 (cDC1s) and promoted cytotoxic CD8+ T cell responses, resulting in efficient clearing of FVC-infected cells. Accordingly, CD169 blockade led to higher viral loads and accelerated death in susceptible mouse strains. Thus, CD169 plays a protective role during FVC pathogenesis by reducing viral dissemination to erythroblasts and eliciting an effective cytotoxic T lymphocyte response via cDC1s

Lewy Body Dementia Association’s Research Centers of Excellence Program: Inaugural Meeting Proceedings

Abstract The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator’s meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), and to create a clinical trials-ready network. Four working groups (WG) were created to pursue the LBDA RCOE aims: (1) increase access to high-quality clinical care, (2) increase access to support for people living with LBD and their caregivers, (3) increase knowledge of LBD among medical and allied (or other) professionals, and (4) create infrastructure for a clinical trials-ready network as well as resources to advance the study of new therapeutics.https://deepblue.lib.umich.edu/bitstream/2027.42/148286/1/13195_2019_Article_476.pd

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia

Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia. These recommendations were developed following the previously established process based on the Institute of Medicine’s clinical practice guidelines. In doing so, a systematic literature search was performed for high-impact studies from 2004 to 2014 and was supplemented with further literature as identified by the panel. The consensus panel met in December of 2014 with the goal to generate consensus recommendations for the clinical use of immunotherapy in patients with hematologic malignancies. During this meeting, consensus panel voting along with discussion were used to rate and review the strength of the supporting evidence from the literature search. These consensus recommendations focus on issues related to patient selection, toxicity management, clinical endpoints, and the sequencing or combination of therapies. Overall, immunotherapy is rapidly emerging as an effective therapeutic strategy for the management of hematologic malignances. Evidence-based consensus recommendations for its clinical application are provided and will be updated as the field evolves

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis.

Aims: Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium. Methods and results: We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4-4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15-1.29] at 5.5 mmol/L and 1.49 (95% CI 1.26-1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin-angiotensin-aldosterone system inhibitor use, and across cohorts. Conclusions: Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials