Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1. Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay. Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques

Options for managing alkaline steel slag leachate: A life cycle assessment

Management of steel slag (a major by-product of the steel industry) includes the treatment of highly alkaline leachate (pH > 11.5) from rainwater infiltration of slag deposits to prevent adverse impact upon surface or ground waters. This study aims to compare different treatment options for steel slag leachate through a life cycle assessment (LCA). Five options were compared: active treatment by acid dosing (A-H2SO4), active treatment by carbon dioxide dosing (A-CO2), active treatment by calcium chloride dosing (A-CaCl2), passive treatment by cascade and reedbeds with pumping (P-P), and passive treatment by cascade and reedbeds in a gravity-driven configuration (P-G). The functional unit was 1 m3 of treated leachate with pH < 9, considering 24 h and 365 days of operating, maintenance operations every year, and service life of 20 years. Inventory data were obtained from project designers, commercial suppliers, laboratory data and field tests. The environmental impacts were calculated in OpenLCA using the ELCD database and ILCD 2011 method, covering twelve impact categories. The A-CaCl2 option scored worse than all other treatments for all considered environmental impact categories. Regarding human toxicity, A-CaCl2 impact was 1260 times higher than the lowest impact option (A-CO2) for carcinogenics and 53 times higher for non-carcinogenics (A-H2SO4). For climate change, the lowest impact was calculated for P-G < P-P < A-H2SO4 < A-CO2 < A-CaCl2, while for particulate matter/respiratory inorganics, the options ranked as follows P-G < P-P < A-CO2 < A-H2SO4 < A-CaCl2. The major contributor to these impact categories was the Solvay process to produce CaCl2. Higher uncertainty was associated with the categories particulate matter formation, climate change and human toxicity, as they are driven by indirect emissions from electricity and chemicals production. Both passive treatment options had better environmental performance than the active treatment options. Potential design measures to enhance environmental performance of the treatments regarding metal removal and recovery are discussed and could inform operational management at active and legacy steel slag disposal sites

The effect of high dose antibiotic impregnated cement on rate of surgical site infection after hip hemiarthroplasty for fractured neck of femur : a protocol for a double-blind quasi randomised controlled trial

Background: Mortality following hip hemiarthroplasty is in the range of 10-40% in the first year, with much attributed to post-operative complications. One such complication is surgical site infection (SSI), which at the start of this trial affected 4.68% of patients in the UK having this operation. Compared to SSI rates of elective hip surgery, at less than 1%, this figure is elevated. The aim of this quasi randomised controlled trial (RCT) is to determine if high dose antibiotic impregnated cement can reduce the SSI in patients at 12-months after hemiarthroplasty for intracapsular fractured neck of femur. Methods: 848 patients with an intracapsular fractured neck of femur requiring a hip hemiarthroplasty are been recruited into this two-centre double-blind quasi RCT. Participants were recruited before surgery and quasi randomised to standard care or intervention group. Participants, statistician and outcome assessors were blind to treatment allocation throughout the study. The intervention consisted of high dose antibiotic impregnated cement consisting of 1 gram Clindamycin and 1 gram of Gentamicin. The primary outcome is Health Protection Agency (HPA) defined deep surgical site infection at 12 months. Secondary outcomes include HPA defined superficial surgical site infection at 30 days, 30 and 90-day mortality, length of hospital stay, critical care stay, and complications. Discussion: Large randomised controlled trials assessing the effectiveness of a surgical intervention are uncommon, particularly in the speciality of orthopaedics. The results from this trial will inform evidence-based recommendations for antibiotic impregnated cement in the management of patients with a fractured neck of femur undergoing a hip hemiarthroplasty. If high dose antibiotic impregnated cement is found to be an effective intervention, implementation into clinical practice could improve long-term outcomes for patients undergoing hip hemiarthroplasty

Retrieval of individual patient data depended on study characteristics : a randomized controlled trial

OBJECTIVE: To examine the effect of providing a financial incentive to authors of randomized clinical trials (RCTs) to obtain individual patient data (IPD). STUDY DESIGN AND SETTING: Parallel-group RCT with authors identified in the RCTs eligible for two systematic reviews. The authors were randomly allocated to the intervention (financial incentive with several contact approaches) or control group (using the same contact approaches). Studied outcomes: proportion of authors who provided IPD, time to obtain IPD, and completeness of IPD received. RESULTS: Of the 129 authors contacted, 37 authors suggested or contacted a person/funder providing relevant details or showed interest to collaborate, while 45 authors directed us to contact a person/funder, lacked resources/time, did not have ownership/approval to share the IPD, or claimed IPD was too old. None of the authors shared their IPD. We contacted 17 sponsors and received two complete IPD datasets from one sponsor. The time to obtain IPD was >1 year after a sponsor's positive response. Common barriers included study identification, data ownership, limited data access, and required IPD licenses. CONCLUSIONS: IPD sharing may depend on study characteristics, including funding type, study size, study risk of bias, and treatment effect, but not on providing a financial incentive. TRIAL REGISTRATION: Clinical Trials.gov (NCT02569411), registered on October 5th, 2015

Increasing Short-Stay Unplanned Hospital Admissions among Children in England; Time Trends Analysis '97-'06

BACKGROUND: Timely care by general practitioners in the community keeps children out of hospital and provides better continuity of care. Yet in the UK, access to primary care has diminished since 2004 when changes in general practitioners' contracts enabled them to 'opt out' of providing out-of-hours care and since then unplanned pediatric hospital admission rates have escalated, particularly through emergency departments. We hypothesised that any increase in isolated short stay admissions for childhood illness might reflect failure to manage these cases in the community over a 10 year period spanning these changes. METHODS AND FINDINGS: We conducted a population based time trends study of major causes of hospital admission in children 2 days. By 2006, 67.3% of all unplanned admissions were isolated short stays <2 days. The increases in admission rates were greater for common non-infectious than infectious causes of admissions. CONCLUSIONS: Short stay unplanned hospital admission rates in young children in England have increased substantially in recent years and are not accounted for by reductions in length of in-hospital stay. The majority are isolated short stay admissions for minor illness episodes that could be better managed by primary care in the community and may be evidence of a failure of primary care services

Great Expectations: Voluntary Sports Clubs and Their Role in Delivering National Policy for English Sport

“The original publication is available at www.springerlink.com”. Copyright International Society for Third-Sector Research and The Johns Hopkins University. DOI: 10.1007/s11266-009-9095-yVoluntary sports clubs (VSCs) account for about a quarter of all volunteering in England. The volunteers work in a mutual aid, self-production, self-consumption system whose main purpose is identifying and nurturing high-level performers. But the new HMG/Sport England strategies leading to London 2012 expects volunteers to make a major contribution to sustaining and extending participation. The study utilized six focus group sessions with a total of 36 officials and members of 36 clubs across the six counties of Eastern England to assess whether and to what extent government policy objectives can be delivered through the voluntary sector. The study focused on the perceptions and attitudes of club members about being expected to serve public policy and the current pressures they and their clubs face. The results lead the authors to question the appropriateness, sensitivity, and feasibility of current sport policy, particularly the emphasis on VSCs as policy implementers.Peer reviewe

Capturing health and eating status through a nutritional perception screening questionnaire (NPSQ9) in a randomised internet-based personalised nutrition intervention : the Food4Me study

BACKGROUND: National guidelines emphasize healthy eating to promote wellbeing and prevention of non-communicable diseases. The perceived healthiness of food is determined by many factors affecting food intake. A positive perception of healthy eating has been shown to be associated with greater diet quality. Internet-based methodologies allow contact with large populations. Our present study aims to design and evaluate a short nutritional perception questionnaire, to be used as a screening tool for assessing nutritional status, and to predict an optimal level of personalisation in nutritional advice delivered via the Internet. METHODS: Data from all participants who were screened and then enrolled into the Food4Me proof-of-principle study (n = 2369) were used to determine the optimal items for inclusion in a novel screening tool, the Nutritional Perception Screening Questionnaire-9 (NPSQ9). Exploratory and confirmatory factor analyses were performed on anthropometric and biochemical data and on dietary indices acquired from participants who had completed the Food4Me dietary intervention (n = 1153). Baseline and intervention data were analysed using linear regression and linear mixed regression, respectively. RESULTS: A final model with 9 NPSQ items was validated against the dietary intervention data. NPSQ9 scores were inversely associated with BMI (β = -0.181, p < 0.001) and waist circumference (Β = -0.155, p < 0.001), and positively associated with total carotenoids (β = 0.198, p < 0.001), omega-3 fatty acid index (β = 0.155, p < 0.001), Healthy Eating Index (HEI) (β = 0.299, p < 0.001) and Mediterranean Diet Score (MDS) (β = 0. 279, p < 0.001). Findings from the longitudinal intervention study showed a greater reduction in BMI and improved dietary indices among participants with lower NPSQ9 scores. CONCLUSIONS: Healthy eating perceptions and dietary habits captured by the NPSQ9 score, based on nine questionnaire items, were associated with reduced body weight and improved diet quality. Likewise, participants with a lower score achieved greater health improvements than those with higher scores, in response to personalised advice, suggesting that NPSQ9 may be used for early evaluation of nutritional status and to tailor nutritional advice. TRIAL REGISTRATION: NCT01530139 .Peer reviewedFinal Published versio

Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 : Elaboration and explanation

Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to assess for the presence of selective reporting against completed reviews, when made publicly available, reduce duplication of efforts and potentially prompt collaboration. Evidence documenting the existence of selective reporting and excessive duplication of reviews on the same or similar topics is accumulating and many calls have been made in support of the documentation and public availability of review protocols. Several efforts have emerged in recent years to rectify these problems, including development of an international register for prospective reviews (PROSPERO) and launch of the first open access journal dedicated to the exclusive publication of systematic review products, including protocols (BioMed Central's Systematic Reviews). Furthering these efforts and building on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, an international group of experts has created a guideline to improve the transparency, accuracy, completeness, and frequency of documented systematic review and meta-analysis protocols-PRISMA-P (for protocols) 2015. The PRISMA-P checklist contains 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol. This PRISMA-P 2015 Explanation and Elaboration paper provides readers with a full understanding of and evidence about the necessity of each item as well as a model example from an existing published protocol. This paper should be read together with the PRISMA-P 2015 statement. Systematic review authors and assessors are strongly encouraged to make use of PRISMA-P when drafting and appraising review protocols

Crop Updates 2000 - Weeds

This session covers thirty six papers from different authors: INTRODUCTION, Vanessa Stewart Agriculture Western Australia INTEGRATED WEED MANAGEMENT Effect of seeding density, row spacing and Trifluralin on the competitive ability of Annual Ryegrass in a minimum tillage system, David Minkey, Abul Hashem, Glen Riethmuller and Martin Harries, Agriculture Western Australia High wheat seeding rates coupled with narrow row spacing increases yield and suppresses grass, Peter Newman1 and Cameron Weeks2,1Agronomist, Elders Limited 2Mingenew/Irwin Group Resistant ryegrass management in a wheat – lupin rotation, Abul Hashem, Harmohinder S. Dhammu, Aik Cheam, David Bowran and Terry Piper, Agriculture Western Australia Integrated weed management – Will it work with my rotation? Alexandra Wallace, Agriculture Western Australia Long term herbicide resistance trial – Mingenew, Peter Newman Elders, Cameron Weeks Mingenew-Irwin Group Is two years enough? Bill Roy, Agricultural Consulting and Research Services The fate of ryegrass seed when sheep graze chaff cart heaps, Keith L. Devenish1 and Lisa J. Leaver2 1 Agriculture Western Australia, 2Curtin University of Technology, Muresk Institute of Agriculture Can blanket wiping and crop topping prevent seed set of resistant wild radish and mustard? StAbul Hashem, Harmohinder Dhammu, Vanessa Stewart, Brad Rayner and Mike Collins, Agriculture Western Australia The value of green manuring in the integrated management of ryegrass, Marta Monjardino1,2, David Pannell2, Stephen Powles1 ,1Western Australia Herbicide Resistance Initiative, 2Agricultural and Resource Economics, University of Western Australia Some ways of increasing wheat competitiveness against ryegrass,, Mike Collins Centre for Cropping Systems, Agriculture Western Australia WEED BIOLOGY Understanding and driving weed seed banks to very low levels, Sally Peltzer, Agriculture Western Australi HERBICIDE RESISTANCE Cross resistance of chlorsulfuron-resistant wild radish to imidazolinones, Abul Hashem, Harmohinder Dhammu and David Bowran, Agriculture Western Australia Investigation of suspected triazine resistant ryegrass populations for cross-resistance and multiple resistance to herbicides, Michael Walsh, Charles Boyle and Stephen Powles, Western Australian Herbicide Resistance Initiative, University of Western Australia Genetics and fitness of glyphosate resistant ryegrass, S. Powles1, P. Neve1, D. Lorraine-Colwill2, C. Preston2 ,1WAHRI, University of Western Australia 2 CRC Weed Management Systems, University of Adelaide Managing herbicide resistance – the effect of local extinction of resistance genes, Art Diggle1, Paul B. Neve2, Stephen B. Powles2 ,1Agriculture Western Australia, 2WAHRI, Faculty of Agriculture, University of Western Australia The double knock - the best strategy for conserving glyphosate susceptibility? Paul B. Neve1, Art Diggle2, Stephen B. Powles1,1WAHRI, Faculty of Agriculture, University of Western Australia, 2Agriculture Western Australia Wild radish had evolved resistance to triazines, Abul Hashem, Harmohinder S. Dhammu, David Bowran and Aik Cheam, Agriculture Western Australia Ryegrass resistance in Western Australia – where and how much? Rick Llewellyn and Stephen Powles, Western Australian Herbicide Resistance Initiative, Faculty of Agriculture, University of Western Australia Wild radish herbicide resistance survey, Michael Walsh, Ryan Duane and Stephen Powles, Western Australian Herbicide Resistance Initiative, University of Western Australia Knockdown resistance in the Western Australian wheatbelt – a proposed survey, Paul B. Neve1, Abul Hashem2, Stephen B. Powles1,1Western Australian Herbicide Resistance Initiative, University of Western Australia, 2Agriculture Western Australia Diflufenican resistant wild radish, Aik Cheam, Siew Lee, David Bowran, David Nicholson and Abul Hashem, Agriculture Western Australi Multiple resistance to triazines and diflufenican further complicates wild radish control, Aik Cheam, Siew Lee, David Bowran, David Nicholson and Abul Hashem, Agriculture Western Australia HERBICIDE TOLERANCE 25. Herbicide tolerance of lupins, Terry Piper, Weed Science Group, Agriculture Western Australia 26. Tanjil lupins will tolerate metribuzin under the right conditions, Peter Newman, Agronomist Elders Limited and Cameron Weeks, Mingenew/Irwin Group 27. Herbicide damage does not mean lower yield in Lupins, Peter Carlton, Trials Coordinator, Elders Limited 28. Herbicide tolerance of new pea varieties, Dr Terry Piper, Agriculture Western Australia 29. Herbicide tolerance of (waterlogged) wheat, Dr Terry Piper, Agriculture Western Australia 30. Wheat tolerance trials – Mingenew 1999, Peter Newman1, Cameron Weeks2 and Stewart Smith3,1Elders, Mingenew, 2Mingenew-Irwin Group,3Agriculture Western Australia ISSUES OF TRIFLURALIN USE 31. Trifluralin works better on ryegrass when no-tilling into thick wheat stubbles as granules, or mixed with limesand, Bill Crabtree, WANTFA Scientific Officer 32. Increasing trifluralin rate did not compensate for delaying incorporation, Bill Crabtree, WANTFA Scientific Officer 33. Poor emergence survey, 1999, Terry Piper, Weed Science Group, Agriculture Western Australia HERBICIDES – ISSUES AND OPTIONS 34. AFFINITY 400DF – A new herbicide with a new mode of action (Group G) for Broadleaf Weed Control in Cereals, Gordon Cumming, Technical Officer, Crop Care Australasia 35 Herbicide screening for Marshmallow, David Minkey1 and David Cameron2,1Agriculture Western Australia, 2Elders Ltd, Merredin 36. The control of Capeweed in Clearfield Production System for Canola, Mike Jackson and Scott Paton, Cyanamid Agriculture Pty Ltd 37.Effect of herbicides Tordonä 75D and Lontrelä,used for eradication of Skeleton Weed, on production of Lupins I the following seasons, John R. Peirce and Brad J. Rayner, Agriculture Western Australia INDUSTRY PROTECTION 38. Graingaurd – Opportunities for agribusiness to help protect the West Australian grains industry, Greg Shea, Executive Officer, GrainGuard Agriculture Western Australi