Effects of traumatic brain injury and posttraumatic stress disorder on development of Alzheimer's disease in Vietnam Veterans using the Alzheimer's Disease Neuroimaging Initiative: Preliminary report

Introduction Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) have previously been reported to be associated with increased risk of Alzheimer's disease (AD). We are using biomarkers to study Vietnam Veterans with/without mild cognitive impairment with a history of at least one TBI and/or ongoing PTSD to determine whether these contribute to the development of AD. Methods Potential subjects identified by Veterans Administration records underwent an initial telephone screen. Consented subjects underwent clinical evaluation, lumbar puncture, structural magnetic resonance imaging, and amyloid positron emission tomography (PET) scans. Results We observed worse cognitive functioning in PTSD and TBI + PTSD groups, worse global cognitive functioning in the PTSD group, lower superior parietal volume in the TBI + PTSD group, and lower amyloid positivity in the PTSD group, but not the TBI group compared to controls without TBI/PTSD. Medial temporal lobe atrophy was not increased in the PTSD and/or TBI groups. Discussion Preliminary results do not indicate that TBI or PTSD increase the risk for AD measured by amyloid PET. Additional recruitment, longitudinal follow-up, and tau-PET scans will provide more information in the future

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

INTRODUCTION: The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. METHODS: ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. RESULTS: Multimodal analyses will provide insight into AD pathophysiology and disease progression. DISCUSSION: ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments

Impact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) was established in 2004 to facilitate the development of effective treatments for Alzheimer's disease (AD) by validating biomarkers for AD clinical trials. METHODS: We searched for ADNI publications using established methods. RESULTS: ADNI has (1) developed standardized biomarkers for use in clinical trial subject selection and as surrogate outcome measures; (2) standardized protocols for use across multiple centers; (3) initiated worldwide ADNI; (4) inspired initiatives investigating traumatic brain injury and post-traumatic stress disorder in military populations, and depression, respectively, as an AD risk factor; (5) acted as a data-sharing model; (6) generated data used in over 600 publications, leading to the identification of novel AD risk alleles, and an understanding of the relationship between biomarkers and AD progression; and (7) inspired other public-private partnerships developing biomarkers for Parkinson's disease and multiple sclerosis. DISCUSSION: ADNI has made myriad impacts in its first decade. A competitive renewal of the project in 2015 would see the use of newly developed tau imaging ligands, and the continued development of recruitment strategies and outcome measures for clinical trials

Prospects for observing and localizing gravitational-wave transients with advanced LIGO and advanced virgo

We present a possible observing scenario for the Advanced LIGO and Advanced Virgo gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We determine the expected sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron-star systems, which are considered the most promising for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5 deg^2 to 20 deg^2 will require at least three detectors of sensitivity within a factor of ~2 of each other and with a broad frequency bandwidth. Should the third LIGO detector be relocated to India as expected, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone

Crop Updates 2009 - Cereals

This session covers twenty seven papers from different authors: PLENARY 1. Building soil carbon for productivity and implications for carbon accounting, Jeff Baldock, CSIRO Land and Water, Adelaide, SA 2. Fact or Fiction: Who is telling the truth and how to tell the difference, Doug Edmeades, agKnowledge Ltd, Hamilton 3. Four decades of crop sequence trials in Western Australia, Mark Seymour,Department of Agriculture and Food BREAK CROPS 4. 2008 Break Crops survey Report, Paul Carmody,Development Officer, Department of Agriculture and Food 5. Attitudes of Western Australian wheatbelt growers to ‘Break Crops’, Paul Carmody and Ian Pritchard, Development Officers, Department of Agriculture and Food 6. The value of organic nitrogen from lupins, Alan Meldrum, Pulse Australia 7.The area of break crops on farm: What farmers are doing compared to estimates based on maximising profit, Michael Robertson and Roger Lawes,CSIRO Floreat, Rob Sands,FARMANCO Farm Consultants, Peter White,Department of Agriculture and Food, Western Australia, Felicity Byrne and Andrew Bathgate,Farming Systems Analysis CROP SPECIFIC Breeding 8. Identification of WALAB2014 as a potential albus lupin variety for northern agricultural region of Western Australia, Kedar Adhikari, Department of Agriculture and Food 9. Enhancement of black spot resistance in field pea, Kedar Adhikari, Tanveer Khan, Stuart Morgan and Alan Harris, Department of Agriculture and Food 10. Desi chickpea breeding: Evaluation of advanced line, Khan, TN1, Harris, A1, Gaur, P2, Siddique, KHM3, Clarke, H4, Turner, NC4, MacLeod, W1, Morgan, S1 1Department of Agriculture and Food, Western Australia, 2International Crop Research Institute for the Semi Arid Tropics (ICRISAT), 3The University of Western Australia, 4Centre for Legumes in Mediterranean Agriculture 11. Pulse Breeding Australia-Australian Field Pea Improvement Program (AFPIP), Ian Pritchard1, Chris Veitch1, Stuart Morgan1, Alan Harris1 and Tony Leonforte 2 1 Department of Agriculture and Food, Western Australia, 2 Department off Primary Industries, Victoria Disease 12. Interaction between wheat varieties and fungicides to control stripe rust for grain and quality, Kith Jayasena, Geoff Thomas, Rob Loughman, Kazue Tanaka and Bill MacLeod, Department of Agriculture and Food 13. Findings of canola disease survey 2008 and its implications for better disease management in 2009, Ravjit Khangura, WJ MacLeod, P White, P Carmody and M Amjad, Department of Agriculture and Food 14. Combating wheat leaf diseases using genome sequencing and functional genomics, Richard Oliver, Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University 15. Distribution and survival of wheat curl mite (Aceria tosichella), vector of Wheat Streak Mosaic Virus, in the WA grainbelt during 2008, Dusty Severtson, Peter Mangano, John Botha and Brenda Coutts, Department of Agriculture and Food 16. Partial resistance to Stagonspora (Septoria) Partial resistance to Stagonospora (Septoria) nodorum blotch and response to fungicide in a severe epidemic scenario, Manisha Shankar1, Richard Oliver2, Kasia Rybak2and Rob Loughman1 1Department of Agriculture and Food, Western Australia, 2Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University, Western Australia 17. Black pod syndrome in lupins can be reduced by regular insecticide sprays, Peter White and Michael Baker,Department of Agriculture and Food Variety performance 18. Incorporating new herbicide tolerant juncea canola into low rainfall cropping systems in Western Australia, Mohammad Amjad, Department of Agriculture and Food 19. Varietal differences in germ end staining of barley, Andrea Hills,Department of Agriculture and Food 20. Wheat variety performance in the Central Agricultural Region in 2008, Shahajahan Miyan, Department of Agriculture and Food 21. Barley variety identification using DNA fingerprinting, Peter Portmann, Agriconnect, Perth WA Dr Nicole Rice, Southern Cross University, Lismore NSW Prof Robert Henry, Southern Cross University, Lismore NSW 22. Forecast disease resistance profile for the Western Australian barley crop over the next three years, Jeff J. Russell, Department of Agriculture and Food 23. Malting barley varieties differ in their flowering date and their response to changes in sowing date, BH Paynter and Jeff J. Russell,Department of Agriculture and Food 24. Market development for new barley varieties, Linda Price,Barley Australia 25. Response of wheat varieties to sowing time at Mt Barker, Katanning and Newdegate in 2008, Brenda Shackley and Vicki Scanlan,Department of Agriculture and Food 26. Flowering dates of wheat varieties in 2008 at three locations in Western Australia, Darshan Sharma, Brenda Shackley and Christine Zaicou-Kunesch, Department of Agriculture and Food 27. Agronomic responses of new wheat varieties in the norther agricultural region in 2008, Christine Zaicou-Kunesch, Department of Agriculture and Foo

Detection of β-amyloid positivity in Alzheimer’s Disease Neuroimaging Initiative participants with demographics, cognition, MRI and plasma biomarkers

In vivo gold standard for the ante-mortem assessment of brain β-amyloid pathology is currently β-amyloid positron emission tomography or cerebrospinal fluid measures of β-amyloid42 or the β-amyloid42/β-amyloid40 ratio. The widespread acceptance of a biomarker classification scheme for the Alzheimer's disease continuum has ignited interest in more affordable and accessible approaches to detect Alzheimer's disease β-amyloid pathology, a process that often slows down the recruitment into, and adds to the cost of, clinical trials. Recently, there has been considerable excitement concerning the value of blood biomarkers. Leveraging multidisciplinary data from cognitively unimpaired participants and participants with mild cognitive impairment recruited by the multisite biomarker study of Alzheimer's Disease Neuroimaging Initiative, here we assessed to what extent plasma β-amyloid42/β-amyloid40, neurofilament light and phosphorylated-tau at threonine-181 biomarkers detect the presence of β-amyloid pathology, and to what extent the addition of clinical information such as demographic data, APOE genotype, cognitive assessments and MRI can assist plasma biomarkers in detecting β-amyloid-positivity. Our results confirm plasma β-amyloid42/β-amyloid40 as a robust biomarker of brain β-amyloid-positivity (area under curve, 0.80-0.87). Plasma phosphorylated-tau at threonine-181 detected β-amyloid-positivity only in the cognitively impaired with a moderate area under curve of 0.67, whereas plasma neurofilament light did not detect β-amyloid-positivity in either group of participants. Clinical information as well as MRI-score independently detected positron emission tomography β-amyloid-positivity in both cognitively unimpaired and impaired (area under curve, 0.69-0.81). Clinical information, particularly APOE ε4 status, enhanced the performance of plasma biomarkers in the detection of positron emission tomography β-amyloid-positivity by 0.06-0.14 units of area under curve for cognitively unimpaired, and by 0.21-0.25 units for cognitively impaired; and further enhancement of these models with an MRI-score of β-amyloid-positivity yielded an additional improvement of 0.04-0.11 units of area under curve for cognitively unimpaired and 0.05-0.09 units for cognitively impaired. Taken together, these multi-disciplinary results suggest that when combined with clinical information, plasma phosphorylated-tau at threonine-181 and neurofilament light biomarkers, and an MRI-score could effectively identify β-amyloid+ cognitively unimpaired and impaired (area under curve, 0.80-0.90). Yet, when the MRI-score is considered in combination with clinical information, plasma phosphorylated-tau at threonine-181 and plasma neurofilament light have minimal added value for detecting β-amyloid-positivity. Our systematic comparison of β-amyloid-positivity detection models identified effective combinations of demographics, APOE, global cognition, MRI and plasma biomarkers. Promising minimally invasive and low-cost predictors such as plasma biomarkers of β-amyloid42/β-amyloid40 may be improved by age and APOE genotype

Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana

Transketolase (TKT) is part of the non-oxidative branch of the pentose phosphate pathway (PPP). Here we describe the impact of removing this enzyme from the pathogenic protozoan Leishmania mexicana. Whereas the deletion had no obvious effect on cultured promastigote forms of the parasite, the Δtkt cells were not infective to mice. Δtkt promastigotes were more susceptible to oxidative stress and various leishmanicidal drugs than wild-type, and metabolomics analysis revealed profound changes to metabolism in these cells. In addition to changes consistent with those directly related to the role of TKT in the PPP, central carbon metabolism was substantially decreased, the cells consumed significantly less glucose, flux through glycolysis diminished, and production of the main end products of metabolism was decreased. Only minor changes in RNA abundance from genes encoding enzymes in central carbon metabolism, however, were detected although fructose-1,6-bisphosphate aldolase activity was decreased two-fold in the knock-out cell line. We also showed that the dual localisation of TKT between cytosol and glycosomes is determined by the C-terminus of the enzyme and by engineering different variants of the enzyme we could alter its sub-cellular localisation. However, no effect on the overall flux of glucose was noted irrespective of whether the enzyme was found uniquely in either compartment, or in both

Crop Updates 2010 - Crop Specific

This session covers twenty four papers from different authors: PLENARY 1. Challenges facing western Canadian cropping over the next 10 years, Hugh J Beckie, Research Centre, Agriculture and Agri-Food Canada, Saskatoon, Saskatchewan CROP SPECIFIC Breeding 2. The challenge of breeding canola hybrids – new opportunities for WA growers, Wallace Cowling, Research Director, Canola Breeders Western Australia Pty Ltd 3. Chickpea 2009 crop variety testing of germplasm developed by DAFWA/CLIMA/ICRISAT/COGGO alliance. Khan, TN1,3, Adhikari, K1,3, Siddique, K2, Garlinge, J1, Smith, L1, Morgan, S1 and Boyd, C1 1Department of Agriculture and Food, Western Australia (DAFWA), 2Insititute of Agriculture, The University of Western Australia (UWA), 3Centre for Legumes in Mediterranean Agriculture (CLIMA), The University of Western Australia 4. PBA Pulse Breeding Australia – 2009 Field Pea Results, Ian Pritchard1, Chris Veitch1, Colin Boyd1, Stuart Morgan1, Alan Harris1 and Tony Leonforte2, 1Department of Agriculture and Food, Western Australia, 2Department of Primary Industries, Victoria 5. PBA Pulse Breeding Australia – 2009 Chickpea Results, Ian Pritchard1, Chris Veitch1, Colin Boyd1, Murray Blyth1, Shari Dougal1 and Kristy Hobson2 1Department of Agriculture and Food, Western Australia, 2Department of Primary Industries, Victoria Decision Support 6. A tool for identifying problems in wheat paddocks, Ben Curtis and Doug Sawkins, Department of Agriculture and Food 7. DAFWA Seasonal Forecast for 2010, Stephens, D, Department of Agriculture and Food, Western Australian, Climate and Modelling Group Disease 8. Enhancement of black spot resistance in field pea, Kedar Adhikari, T Khan, S Morgan and C Boyd, Department of Agriculture and Food, 9. fungicide management of yellow spot in wheat, Ciara Beard, Kith Jayasena, Kazue Tanaka and Anne Smith, Department of Agriculture and Food 10. Resistance to infection by Beet western yellows virus in four Australian canola varieties, Brenda Coutts and Roger Jones, Department of Agriculture and Food 11. Yellow spot carryover risk from stubble in wheat-on-wheat rotations, Jean Galloway, Pip Payne and Tess Humphreys, Department of Agriculture and Food 12. Fungicides for the future: Management of Barley Powdery Mildew and Leaf Rust, Kith Jayasena, Kazue Tanaka and William MacLeod, Department of Agriculture and Food 13. 2009 canola disease survey and management options for blackleg and Sclerotinia in 2010, Ravjit Khangura, WJ MacLeod, M Aberra and H Mian, Department of Agriculture and Food 14. Impact of variety and fungicide on carryover of stubble borne inoculum and yellow spot severity in continuous wheat cropping, Geoff Thomas, Pip Payne, Tess Humphreys and Anne Smith, Department of Agriculture and Food 15. Limitations to the spread of Wheat streak mosaic virus by the Wheat curl mite in WA during 2009, Dusty Severtson, Peter Mangano, Brenda Coutts, Monica Kehoe and Roger Jones, Department of Agriculture and Food 16. Viable solutions for barley powdery mildew, Madeline A. Tucker, Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University Marketing 17. The importance of varietal accreditation in a post-deregulation barley marketing environment, Neil Barker, Barley Australia 18. Can Australia wheat meet requirements for a new middle east market? Robert Loughman, Larisa Cato, Department of Agriculture and Food, and Ken Quail, BRI Australia VARIETY PERFORMANCE 19. Sowing rate and time for hybrid vs open-pollinated canola, Mohammad Amjad and Mark Seymour, Department of Agriculture and Food 20. HYOLA® National Hybrid vs OP Canola Hybrid F1 vs Retained Seed Generation Trial Results and recommendations for growers, Justin Kudnig, Mark Thompson, Anton Mannes, Michael Uttley, Chris Fletcher, Andrew Etherton, Nick Joyce and Kate Light, Pacific Seeds Australia 21. HYOLA® National Hybrid vs OP Canola Sowing Rate Trial Results and plant population recommendations for Australian growers, Justin Kudnig, Mark Thompson, Anton Mannes, Michael Uttley, Andrew Etherton, Chris Fletcher, Nick Joyce and Kate Light, Pacific Seeds Australia; Peter Hamblin, Agritech Research Young, NSW, Michael Lamond, Agrisearch, York, Western Australia 22. Desi chickpea agronomy for 2010, Alan Meldrum, Pulse Australia and Wayne Parker, Department of Agriculture and Food 23. New wheat varieties – exploit the benefits and avoid the pitfalls, Steve Penny, Sarah Ellis, Brenda Shackley, Christine Zaicou, Shahajahan Miyan, Darshan Sharma and Ben Curtis, Department of Agriculture and Food 24. The influence of genetics and environment on the level of seed alkaloid in narrow-leafed lupins, Greg Shea1, Bevan Buirchell1, David Harris2 and Bob French1, 1Department of Agriculture and Food, 2ChemCentr

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes