Estimating vitamin C intake requirements in diabetes mellitus : Analysis of NHANES 2017-2018 and EPIC-Norfolk cohorts

Acknowledgments We would like to acknowledge the principal investigators and staff of the EPIC-Norfolk study. We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. Funding The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1, MC-UU-12015/1 and MC-UU-00006/1) and Cancer Research UK (C864/A14136).Peer reviewedPublisher PD

Helen Harriet Salls Correspondence

Entries include handwritten letters from Salls on La Grange College, La Grange, Georgia, stationery and from North Carolina concerning book gifts and a poetry brochure produced with her sister Grace in 1921, typed notes on publication and excerpts of correspondence from Lunt on Auburn Public Library, Auburn, Maine, stationery, handwritten notes concerning University of North Carolina librarian Thornton and this library collection, and a publisher advertisement and book order form concerning her college dedication verse with handwritten biographical notes concerning editor Wightman F. Melton

Validity of a three-variable juvenile arthritis disease activity score in children with new-onset juvenile idiopathic arthritis

<p>Objectives To investigate the validity and feasibility of the Juvenile Arthritis Disease Activity Score (JADAS) in the routine clinical setting for all juvenile idiopathic arthritis (JIA) disease categories and explore whether exclusion of the erythrocyte sedimentation rate (ESR) from JADAS (the ‘JADAS3’) influences correlation with single markers of disease activity.</p> <p>Methods JADAS-71, JADAS-27 and JADAS-10 were determined at baseline for an inception cohort of children with JIA in the Childhood Arthritis Prospective Study. JADAS3-71, JADAS3-27 and JADAS3-10 were determined using an identical formula but with exclusion of ESR. Correlation of JADAS with JADAS3 and single measures of disease activity/severity were determined by category.</p> <p>Results Of 956 eligible children, sufficient data were available to calculate JADAS-71, JADAS-27 and JADAS-10 at baseline in 352 (37%) and JADAS3 in 551 (58%). The median (IQR) JADAS-71, JADAS-27 and JADAS-10 for all 352 children was 11 (5.9–18), 10.4 (5.7–17) and 11 (5.9–17.3), respectively. Median JADAS and JADAS3 varied significantly with the category (Kruskal–Wallis p=0.0001), with the highest values in children with polyarticular disease patterns. Correlation of JADAS and JADAS3 across all categories was excellent. Correlation of JADAS71 with single markers of disease activity/severity was good to moderate, with some variation across the categories. With the exception of ESR, correlation of JADAS3-71 was similar to correlation of JADAS-71 with the same indices.</p> <p>Conclusions This study is the first to apply JADAS to all categories of JIA in a routine clinical setting in the UK, adding further information about the feasibility and construct validity of JADAS. For the majority of categories, clinical applicability would be improved by exclusion of the ESR.</p&gt

Biologic treatment response among adults with juvenile idiopathic arthritis: results from the British Society for Rheumatology Biologics Register

Abstract Objective. To describe the use of and response to biologic therapies commenced in adults with JIA. Methods. Patients with arthritis onset <16 years were identified from the British Society for Rheumatology Biologics Register for rheumatoid arthritis (BSRBR-RA) and stratified into ILAR JIA subtypes. Patterns of biologic use and treatment persistence were explored, with disability levels (HAQ) and remission rates [28-Joint Disease Activity Score (DAS28)] evaluated at 6 and 12 months. Results. Arthritis with an onset of <16 years was confirmed in 225 patients and the ILAR subtype was determined in 154 (68%). Only 58 (26%) patients had a diagnosis of JIA recorded in the BSRBR-RA. The median age at biologic commencement was 31 years [interquartile range (IQR) 2339] and 76% were female. The biologic therapies were etanercept (49%), infliximab (28%), adalimumab (22%) and anakinra (1%). Fifty per cent of patients received more than one biologic during follow-up (2 agents, n = 64; 53 agents, n = 49). Treatment persistence at 1 year was 78% (95% CI 71%, 82%), falling to 42% (95% CI 34%, 49%) at 5 years. Both the HAQ and DAS28 improved significantly at 6 months, with 21% and 28% of patients in remission (DAS28 < 2.6) at 6 and 12 months, respectively. Conclusion. This study describes patterns and identifies outcomes of biologic use in a national cohort of adults with JIA. With no national guidance currently available in this area, the choice of first biologic was inconsistent, although treatment outcomes were good. These data confirm that biologic therapies are an important treatment option in adults with active JIA in adulthood

Developing a Standard Set of Patient-Centred Outcomes for Inflammatory Bowel Disease—an International, Cross-disciplinary Consensus

Success in delivering value-based healthcare involves measuring outcomes that matter most to patients. Our aim was to develop a minimum Standard Set of patient-centred outcome measures for inflammatory bowel disease (IBD), for use in different healthcare settings.An international working group (n=25) representing patients, patient associations, gastroenterologists, surgeons, specialist nurses, IBD registries and patient-reported outcome measure (PROM) methodologists participated in a series of teleconferences incorporating a modified Delphi process. Systematic review of existing literature, registry data, patient focus groups and open review periods were used to reach consensus on a minimum set of standard outcome measures and risk adjustment variables. Similar methodology has been used in 21 other disease areas (www.ichom.org).A minimum Standard Set of outcomes was developed for patients (aged ≥16) with IBD. Outcome domains included survival and disease control (survival, disease activity/remission, colorectal cancer, anaemia), disutility of care (treatment-related complications), healthcare utilisation (IBD-related admissions, emergency room visits) and patient-reported outcomes (including quality of life, nutritional status and impact of fistulae) measured at baseline and at 6 or 12 month intervals. A single PROM (IBD-Control questionnaire) was recommended in the Standard Set and minimum risk adjustment data collected at baseline and annually were included: demographics, basic clinical information and treatment factors.A Standard Set of outcome measures for IBD has been developed based on evidence, patient input and specialist consensus. It provides an international template for meaningful, comparable and easy-to-interpret measures as a step towards achieving value-based healthcare in IBD

Neuropsychological functioning and jumping to conclusions in delusions

Background: It has been consistently demonstrated that delusions are related to jumping to conclusions (JTC), a data-gathering bias and potential candidate endophenotype of psychosis. Recent research suggests that JTC may be a marker of treatment response. However, we know little about the factors contributing to the occurrence of this reasoning bias. This study investigated the relationship between JTC and hypothesised deficits in working memory, employing standard well-validated neuropsychological tests, in people with current delusions. Method: One hundred and twenty six people with schizophrenia spectrum psychosis and current delusions were assessed for current symptoms, and tested for JTC. We compared performance on tests of working memory in those with the reasoning bias and those without. Results: As expected, 30–40% of this sample of people with current delusions showed the JTC bias. There were no differences in premorbid IQ between those with and without the JTC reasoning bias. However, the performance of the JTC group was significantly worse on tests of working memory. Conclusions: The JTC data-gathering bias is associated with impairments in working memory. New non-pharmacological interventions for people with delusions, designed to improve data gathering, may benefit from incorporating strategies to overcome deficits in working memory

Glucose utilization via glycogen phosphorylase sustains proliferation and prevents premature senescence in cancer cells.

Metabolic reprogramming of cancer cells provides energy and multiple intermediates critical for cell growth. Hypoxia in tumors represents a hostile environment that can encourage these transformations. We report that glycogen metabolism is upregulated in tumors in vivo and in cancer cells in vitro in response to hypoxia. In vitro, hypoxia induced an early accumulation of glycogen, followed by a gradual decline. Concordantly, glycogen synthase (GYS1) showed a rapid induction, followed by a later increase of glycogen phosphorylase (PYGL). PYGL depletion and the consequent glycogen accumulation led to increased reactive oxygen species (ROS) levels that contributed to a p53-dependent induction of senescence and markedly impaired tumorigenesis in vivo. Metabolic analyses indicated that glycogen degradation by PYGL is important for the optimal function of the pentose phosphate pathway. Thus, glycogen metabolism is a key pathway induced by hypoxia, necessary for optimal glucose utilization, which represents a targetable mechanism of metabolic adaptation

The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort: an important resource for translational research in soft tissue sarcoma

BACKGROUND: Despite high metastasis rates, adjuvant/neoadjuvant systemic therapy for localised soft tissue sarcoma (STS) is not used routinely. Progress requires tailoring therapy to features of tumour biology, which need exploration in well-documented cohorts. Hypoxia has been linked to metastasis in STS and is targetable. This study evaluated hypoxia prognostic markers in the phase III adjuvant radiotherapy VorteX trial. METHODS: Formalin-fixed paraffin-embedded tumour biopsies, fresh tumour/normal tissue and blood were collected before radiotherapy. Immunohistochemistry for HIF-1α, CAIX and GLUT1 was performed on tissue microarrays and assessed by two scorers (one pathologist). Prognostic analysis of disease-free survival (DFS) used Kaplan-Meier and Cox regression. RESULTS: Biobank and outcome data were available for 203 out of 216 randomised patients. High CAIX expression was associated with worse DFS (hazard ratio 2.28, 95% confidence interval: 1.44-3.59, P<0.001). Hypoxia-inducible factor-1α and GLUT1 were not prognostic. Carbonic anhydrase IX remained prognostic in multivariable analysis. CONCLUSIONS: The VorteX-Biobank contains tissue with linked outcome data and is an important resource for research. This study confirms hypoxia is linked to poor prognosis in STS and suggests that CAIX may be the best known marker. However, overlap between single marker positivity was poor and future work will develop an STS hypoxia gene signature to account for tumour heterogeneity

Concurrent Oral 1 - Rheumatoid Arthritis: Treatment [OP4-OP9]: OP4. Inhibition of Radiographic Progression and Improvements in Physical Function at 2 Years, with Increasing Clinical Efficacy Over Time, in Rheumatoid Arthritis (Ra) Patients Treated with Tocilizumab (Tcz): The Lithe Study

Background: Patients with moderate to severe RA who remained on methotrexate (MTX) despite inadequate response were treated with TCZ in a double-blind, randomized, controlled phase 3 trial. Results of a 2-year planned analysis from this study are presented. Methods: Patients were randomized to treatment with TCZ 4 mg/kg + MTX (TCZ4), TCZ 8 mg/kg + MTX (TCZ8) or placebo + MTX (CON) every 4 weeks. If patients failed to respond ( 60% of patients and the DAS28 remission (DAS28 < 2.6) rate was 48% at week 52 and continued to increase to week 104. By week 52, patients treated with TCZ8 had clinically significant improvements in SJC that were maintained through week 104. Rates per 100 PY for adverse events (AEs) were higher in TCZ8 and TCZ4 (263.6, 275.4) vs CON patients (251.4) while rates for serious AEs were comparable (11.4, 12.1, 10.9, respectively). Rates per 100 PY of AEs leading to withdrawal (7.4, 32.5, 4.8) and treatment modification (8.4, 30.7, 20.4) were higher in TCZ8 and TCZ4 vs CON patients, respectively and death rates were comparable (0.6, 0.2, 0.4). Conclusions: Treatment with TCZ + MTX inhibits radiographic progression over 2 years and improves physical function as shown by DAS28 remission, LDAS and low SJC, with a manageable safety profile. Disclosure statement: E.A., F. Hoffmann-La Roche - Employee. P.A., F. Hoffmann-La Roche - Employee. R.B.-V., F. Hoffmann-La Roche - Honoraria. R.F., Genentech - Research Funding, Honoraria. J.K., F. Hoffmann-La Roche - Research funding, Honorari

Crop Updates 2007 - Lupins, Pulses and Oilseeds

This session covers forty eight papers from different authors: 2006 REGIONAL ROUNDUP 1. South east agricultural region, Mark Seymour1 and Jacinta Falconer2, 1Department of Agriculture and Food, 2Cooperative Bulk Handling Group 2. Central agricultural region, Ian Pritchard, Department of Agriculture and Food 3. Great Southern and Lakes region, Rodger Beermier, Department of Agriculture and Food 4. Northern agricultural region, Wayne Parker and Martin Harries, Department of Agriculture and Food LUPINS 5. Development of anthracnose resistant and early flowering albus lupins (Lupinus albus L) in Western Australia, Kedar Adhikari and Geoff Thomas, Department of Agriculture and Food 6. New lupins adapted to the south coast, Peter White, Bevan Buirchell and Mike Baker, Department of Agriculture and Food 7. Lupin species and row spacing interactions by environment, Martin Harries, Peter White, Bob French, Jo Walker, Mike Baker and Laurie Maiolo, Department of Agriculture and Food 8. The interaction of lupin species row spacing and soil type, Martin Harries, Bob French, Laurie Maiolo and Jo Walker, Department of Agriculture and Food 9. The effects of row spacing and crop density on competitiveness of lupins with wild radish, Bob French and Laurie Maiolo, Department of Agriculture and Food 10. The effect of time of sowing and radish weed density on lupin yield, Martin Harries and Jo Walker, Department of Agriculture and Food 11. Interaction of time of sowing and weed management in lupins, Martin Harries and Jo Walker, Department of Agriculture and Food 12. Delayed sowing as a strategy to manage annual ryegrass, Bob French and Laurie Maiolo, Department of Agriculture and Food 13. Is delayed sowing a good strategy for weed management in lupins? Bob French, Department of Agriculture and Food 14. Lupins aren’t lupins when it comes to simazine, Peter White and Leigh Smith, Department of Agriculture and Food 15. Seed yield and anthracnose resistance of Tanjil mutants tolerant to metribuzin, Ping Si1, Bevan Buirchell1,2 and Mark Sweetingham1,2, 1Centre for Legumes in Mediterranean Agriculture, Australia; 2Department of Agriculture and Food 16. The effect of herbicides on nodulation in lupins, Lorne Mills1, Harmohinder Dhammu2 and Beng Tan1, 1Curtin University of Technology and 2Department of Agriculture and Food 17. Effect of fertiliser placements and watering regimes on lupin growth and seed yield in the central grain belt of Western Australia, Qifu Ma1, Zed Rengel1, Bill Bowden2, Ross Brennan2, Reg Lunt2 and Tim Hilder2, 1Soil Science & Plant Nutrition UWA, 2Department of Agriculture and Food 18. Development of a forecasting model for Bean Yellow Mosaic Virus in lupins, T. Maling1,2, A. Diggle1, D. Thackray1,2, R.A.C. Jones2, and K.H.M. Siddique1, 1Centre for Legumes in Mediterranean Agriculture, The University of Western Australia; 2Department of Agriculture and Food 19. Manufacturing of lupin tempe,Vijay Jayasena1,4, Leonardus Kardono2,4, Ken Quail3,4 and Ranil Coorey1,4, 1Curtin University of Technology, Perth, Australia, 2Indonesian Institute of Sciences (LIPI), Indonesia, 3BRI Australia Ltd, Sydney, Australia, 4Grain Foods CRC, Sydney, Australia 20. The impact of lupin based ingredients in ice-cream, Hannah Williams, Lee Sheer Yap and Vijay Jayasena, Curtin University of Technology, Perth WA 21. The acceptability of muffins substituted with varying concentrations of lupin flour, Anthony James, Don Elani Jayawardena and Vijay Jayasena, Curtin University of Technology, PerthWA PULSES 22. Chickpea variety evaluation, Kerry Regan1, Rod Hunter1, Tanveer Khan1,2and Jenny Garlinge1, 1Department of Agriculture and Food, 2CLIMA, The University of Western Australia 23. Advanced breeding trials of desi chickpea, Khan, T.N.1, Siddique, K.H.M.3, Clarke, H.2, Turner, N.C.2, MacLeod, W.1, Morgan, S.1, and Harris, A.1, 1Department of Agriculture and Food, 2Centre for Legumes in Mediterranean Agriculture, 3TheUniversity of Western Australia 24. Ascochyta resistance in chickpea lines in Crop Variety Testing (CVT) of 2006, Tanveer Khan1 2, Bill MacLeod1, Alan Harris1, Stuart Morgan1and Kerry Regan1, 1Department of Agriculture and Food, 2CLIMA, The University of Western Australia 25. Yield evaluation of ascochyta blight resistant Kabuli chickpeas, Kerry Regan1and Kadambot Siddique2, 1Department of Agriculture and Food, 2Institute of Agriculture, The University of Western Australia 26. Pulse WA Chickpea Industry Survey 2006, Mark Seymour1, Ian Pritchard1, Wayne Parker1and Alan Meldrum2, 1Department of Agriculture and Food, 2Pulse Australia 27. Genes from the wild as a valuable genetic resource for chickpea improvement, Heather Clarke1, Helen Bowers1and Kadambot Siddique2, 1Centre for Legumes in Mediterranean Agriculture, 2Institute of Agriculture, The University of Western Australia 28. International screening of chickpea for resistance to Botrytis grey mould, B. MacLeod1, Dr T. Khan1, Prof. K.H.M. Siddique2and Dr A. Bakr3, 1Department of Agriculture and Food, 2The University of Western Australia, 3Bangladesh Agricultural Research Institute 29. Balance® in chickpea is safest applied post sowing to a level seed bed, Wayne Parker, Department of Agriculture and Food, 30. Demonstrations of Genesis 510 chickpea, Wayne Parker, Department of Agriculture and Food 31. Field pea 2006, Ian Pritchard, Department of Agriculture and Food 32. Field pea variety evaluation, Kerry Regan1, Rod Hunter1, Tanveer Khan1,2 and Jenny Garlinge1, 1Department of Agriculture and Food, 2CLIMA, The University of Western Australia 33. Breeding highlights of the Australian Field Pea Improvement Program (AFPIP),Kerry Regan1, Tanveer Khan1,2, Phillip Chambers1, Chris Veitch1, Stuart Morgan1 , Alan Harris1and Tony Leonforte3, 1Department of Agriculture and Food, 2CLIMA, The University of Western Australia, 3Department of Primary Industries, Victoria 34. Field pea germplasm enhancement for black spot resistance, Tanveer Khan, Kerry Regan, Stuart Morgan, Alan Harris and Phillip Chambers, Department of Agriculture and Food 35. Validation of Blackspot spore release model and testing moderately resistant field pea line, Mark Seymour, Ian Pritchard, Rodger Beermier, Pam Burgess and Leanne Young, Department of Agriculture and Food 36. Yield losses from sowing field pea seed infected with Pea Seed-borne Mosaic Virus, Brenda Coutts, Donna O’Keefe, Rhonda Pearce, Monica Kehoe and Roger Jones, Department of Agriculture and Food 37. Faba bean in 2006, Mark Seymour, Department of Agriculture and Food 38. Germplasm evaluation – faba bean, Mark Seymour1, Terri Jasper1, Ian Pritchard1, Mike Baker1 and Tim Pope1,2, 1Department of Agriculture and Food, , 2CLIMA, The University of Western Australia 39. Breeding highlights of the Coordinated Improvement Program for Australian Lentils (CIPAL), Kerry Regan1, Chris Veitch1, Phillip Chambers1 and Michael Materne2, 1Department of Agriculture and Food, 2Department of Primary Industries, Victoria 40. Screening pulse lentil germplasm for tolerance to alternate herbicides, Ping Si1, Mike Walsh2 and Mark Sweetingham1,3, 1Centre for Legumes in Mediterranean Agriculture, 2West Australian Herbicide Resistance Initiative, 3Department of Agriculture and Food 41. Genomic synteny in legumes: Application to crop breeding, Phan, H.T.T.1, Ellwood, S.R.1, Hane, J.1, Williams, A.1, Ford, R.2, Thomas, S.3 and Oliver R1, 1Australian Centre of Necrotrophic Plant Pathogens, Murdoch University, 2BioMarka, University of Melbourne, 3NSW Department of Primary Industries 42. Tolerance of lupins, chickpeas and canola to Balanceâ(Isoxaflutole) and Galleryâ (Isoxaben), Leigh Smith and Peter White, Department of Agriculture and Food CANOLA AND OILSEEDS 43. The performance of TT Canola varieties in the National Variety Test (NVT),WA,2006,Katie Robinson, Research Agronomist, Agritech Crop Research 44. Evaluation of Brassica crops for biodiesel in Western Australia, Mohammad Amjad, Graham Walton, Pat Fels and Andy Sutherland, Department of Agriculture and Food 45. Production risk of canola in different rainfall zones in Western Australia, Imma Farré1, Michael Robertson2 and Senthold Asseng3, 1Department of Agriculture and Food, 2CSIRO Sustainable Ecosystems, 3CSIRO Plant Industry 46. Future directions of blackleg management – dynamics of blackleg susceptibility in canola varieties, Ravjit Khangura, Moin Salam and Bill MacLeod, Department of Agriculture and Food 47. Appendix 1: Contributors 48. Appendix 2: List of common acronym