B-type natriuretic peptide-guided treatment for heart failure

Background Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B‐type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. Objectives To assess whether treatment guided by serial BNP or NT‐proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. Search methods Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. Selection criteria We included randomised controlled trials of NP‐guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow‐up. Adults treated for heart failure, in both in‐hospital and out‐of‐hospital settings, and trials reporting a clinical outcome were included. Data collection and analysis Two review authors independently selected studies for inclusion, extracted data and evaluated risk of bias. Risk ratios (RR) were calculated for dichotomous data, and pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated for continuous data. We contacted trial authors to obtain missing data. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, we assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. Main results We included 18 randomised controlled trials with 3660 participants (range of mean age: 57 to 80 years) comparing NP‐guided treatment with clinical assessment alone. The evidence for all‐cause mortality using NP‐guided treatment showed uncertainty (RR 0.87, 95% CI 0.76 to 1.01; patients = 3169; studies = 15; low quality of the evidence), and for heart failure mortality (RR 0.84, 95% CI 0.54 to 1.30; patients = 853; studies = 6; low quality of evidence). The evidence suggested heart failure admission was reduced by NP‐guided treatment (38% versus 26%, RR 0.70, 95% CI 0.61 to 0.80; patients = 1928; studies = 10; low quality of evidence), but the evidence showed uncertainty for all‐cause admission (57% versus 53%, RR 0.93, 95% CI 0.84 to 1.03; patients = 1142; studies = 6; low quality of evidence). Six studies reported on adverse events, however the results could not be pooled (patients = 1144; low quality of evidence). Only four studies provided cost of treatment results, three of these studies reported a lower cost for NP‐guided treatment, whilst one reported a higher cost (results were not pooled; patients = 931, low quality of evidence). The evidence showed uncertainty for quality of life data (MD ‐0.03, 95% CI ‐1.18 to 1.13; patients = 1812; studies = 8; very low quality of evidence). We completed a 'Risk of bias' assessment for all studies. The impact of risk of bias from lack of blinding of outcome assessment and high attrition levels was examined by restricting analyses to only low 'Risk of bias' studies. Authors' conclusions In patients with heart failure low‐quality evidence showed a reduction in heart failure admission with NP‐guided treatment while low‐quality evidence showed uncertainty in the effect of NP‐guided treatment for all‐cause mortality, heart failure mortality, and all‐cause admission. Uncertainty in the effect was further shown by very low‐quality evidence for patient's quality of life. The evidence for adverse events and cost of treatment was low quality and we were unable to pool results.</p

Socio-macroeconomic impacts of implementing different post-Brexit UK energy reduction targets to 2030

For the period since 2011, the UK has been bound by European Union (EU) legislation regarding energy reduction targets to 2020. As of 2019, the UK had reduced its final energy use by 18% against a baseline projection to 2020, on track to meet its target of 18%. Whilst the rest of the EU-27 now set their own energy reduction targets to 2030, upon leaving the EU via Brexit, the UK is now free to choose its own energy targets. But what should the energy target be for 2030, and what are the socio-macroeconomic impacts and policy implications? To address this, we use two econometric energy-economy models to assess three different levels of energy reduction target, with 27%, 33% and 40% reduction in 2030 versus the baseline model projections. We find the strictest (40%) energy reduction target could deliver the largest economic and employment benefits. However, careful attention to policies are required, to ensure improvements to overall economy-wide energy efficiency whilst minimising rebound. Demand-side policies of serious scale within an ‘avoid-shift-improve’ framework are required, including massive building retrofits, significant improvements to industrial energy efficiency, switching to low energy transport modes, and moving away from meat-based diets

Past, present, and future of the Living Planet Index

As we enter the next phase of international policy commitments to halt biodiversity loss (e.g., Kunming-Montreal Global Biodiversity Framework), biodiversity indicators will play an important role in forming the robust basis upon which targeted, and time sensitive conservation actions are developed. Population trend indicators are one of the most powerful tools in biodiversity monitoring due to their responsiveness to changes over short timescales and their ability to aggregate species trends from global down to sub-national or even local scale. We consider how the project behind one of the foremost population level indicators - the Living Planet Index - has evolved over the last 25 years, its value to the field of biodiversity monitoring, and how its components have portrayed a compelling account of the changing status of global biodiversity through its application at policy, research and practice levels. We explore ways the project can develop to enhance our understanding of the state of biodiversity and share lessons learned to inform indicator development and mobilise action

Past, present, and future of the Living Planet Index

As we enter the next phase of international policy commitments to halt biodiversity loss (e.g., Kunming-Montreal Global Biodiversity Framework), biodiversity indicators will play an important role in forming the robust basis upon which targeted, and time sensitive conservation actions are developed. Population trend indicators are one of the most powerful tools in biodiversity monitoring due to their responsiveness to changes over short timescales and their ability to aggregate species trends from global down to sub-national or even local scale. We consider how the project behind one of the foremost population level indicators - the Living Planet Index - has evolved over the last 25 years, its value to the field of biodiversity monitoring, and how its components have portrayed a compelling account of the changing status of global biodiversity through its application at policy, research and practice levels. We explore ways the project can develop to enhance our understanding of the state of biodiversity and share lessons learned to inform indicator development and mobilise action

Agribusiness Sheep Updates - 2004 part 2

Precision Pastures Using Species Diversity to Improve Pasture Performance Anyou Liu and Clinton Revell, Department of Agriculture, Western Australia New Annual Pasture Legumes for Sheep Graziers Phil Nichols, Angelo Loi, Brad Nutt and Darryl McClements Department of Agriculture Western Australia Pastures from Space – Can Satellite Estimates of Pasture Growth Rate be used to Increase Farm Profit? Lucy Anderton, Stephen Gherardi and Chris Oldham Department of Agriculture Western Australia Summer-active Perennial Grasses for Profitable Sheep Production Paul Sanford and John Gladman, Department of Agriculture, Western Australia Pastures From Space – Validation Of Predictions Of Pasture Growth Rates DONALD, G.E.A, EDIRISINGHE, A.A, HENRY, D.A.A, MATA, G.A, GHERARDI, S.G.B, OLDHAM, C.M.B, GITTINS, S.P.B AND SMITH, R. C. G.C ACSIRO, Livestock Industries, PMB 5, Wembley, WA, 6913. BDepartment of Agriculture Western Australia, Bentley, WA, 6983. C Department of Land Information Western Australia, Floreat, WA, 6214. Production and Management of Biserrula Pasture - Managing the Risk of Photosensitivity Dr Clinton Revell and Roy Butler, Department of Agriculture Western Australia Meat Quality of Sheep Grazed on a Saltbush-based Pasture Kelly Pearce1,2, David Masters1, David Pethick2, 1 CSIRO LIVESTOCK INDUSTRIES, WEMBLEY, WA 2 SCHOOL OF VETERINARY AND BIOMEDICAL SCIENCE, MURDOCH UNIVERSITY, MURDOCH, WA Precision Sheep Lifetime Wool – Carryover Effects on Subsequent Reproduction of the Ewe Flock Chris Oldham, Department of Agriculture Western Australia Andrew Thompson, Primary Industries Research Victoria (PIRVic), Dept of Primary Industries, Hamilton, Vic Ewe Productivity Trials - a Linked Analysis Ken Hart, Johan Greeff, Department of Agriculture Western Australia, Beth Paganoni, School of Animal Biology, Faculty of Natural and Agricultural Sciences, University of Western Australia. Grain Finishing Systems For Prime Lambs Rachel Kirby, Matt Ryan, Kira Buttler, Department of Agriculture, Western Australia The Effects of Nutrition and Genotype on the Growth and Development, Muscle Biochemistry and Consumer Response to Lamb Meat David Pethick, Department of Veterinary Science, Murdoch University, WA, Roger Heggarty and David Hopkins, New South Wales Agriculture ‘Lifetime Wool’ - Effects of Nutrition During Pregnancy and Lactation on Mortality of Progeny to Hogget Shearing Samantha Giles, Beth Paganoni and Tom Plaisted, Department of Agriculture Western Australia, Mark Ferguson and Darren Gordon, Primary Industries Research Victoria (PIRVic), Dept of Primary Industries, Hamilton, Vic Lifetime Wool - Target Liveweights for the Ewe Flock J. Young, Farming Systems Analysis Service, Kojonup, C. Oldham, Department of Agriculture Western Australia, A. Thompson, Primary Industries Research Victoria (PIRVic), Hamilton, VIC Lifetime Wool - Effects of Nutrition During Pregnancy and Lactation on the Growth and Wool Production of their Progeny at Hogget Shearing B. Paganoni, University of Western Australia, Nedlands WA, C. Oldham, Department of Agriculture Western Australia, M. Ferguson, A. Thompson, Primary Industries Research Victoria (PIRVic), Hamilton, VIC RFID Technology – Esperance Experiences Sandra Brown, Department of Agriculture Western Australia The Role of Radio Frequency Identification (RFID) Technology in Prime Lamb Production - a Case Study. Ian McFarland, Department of Agriculture, Western Australia. John Archer, Producer, Narrogin, Western Australia Win with Twins from Merinos John Milton, Rob Davidson, Graeme Martin and David Lindsay The University of Western Australia Precision Sheep Need Precision Wool Harvesters Jonathan England, Castle Carrock Merinos, Kingston SE, South Australia Business EBVs and Indexes – Genetic Tools for your Toolbox Sandra Brown, Department of Agriculture Western Australia Green Feed Budget Paddock Calculator Mandy Curnow, Department of Agriculture Western Australia Minimising the Impact of Drought - Evaluating Flock Recovery Options using the ImPack Model Karina P. Wood, Ashley K. White, B. Lloyd Davies, Paul M. Carberry, NSW Department of Primary Industries (NSW DPI), Lifetime Wool - Modifying GrazFeed® for WA Mike Hyder, Department of Agriculture Western Australia , Mike Freer, CSIRO Plant Industry, Canberra, A.C.T. , Andrew van Burgel, and Kazue Tanaka, Department of Agriculture Western Australia Profile Calculator – A Way to Manage Fibre Diameter Throughout the Year to Maximise Returns Andrew Peterson, Department of Agriculture, Western Australia Pasture Watch - a Farmer Friendly Tool for Downloading and Analysing Pastures from Space Data Roger Wiese,Fairport Technologies International, South Perth, WA, Stephen Gherardi, BDepartment of Agriculture Western Australia, Gonzalo Mata, CCSIRO, Livestock Industries, Wembley, Western Australia, and Chris Oldham, Department of Agriculture Western Australia Sy Sheep Cropping Systems An Analysis of a Cropping System Containing Sheep in a Low Rainfall Livestock System. Evan Burt, Amanda Miller, Anne Bennett, Department of Agriculture, Western Australia Lucerne-based Pasture for the Central Wheatbelt – is it Good Economics? Felicity FluggeA, Amir AbadiA,B and Perry DollingA,B,A CRC for Plant-based Management of Dryland Salinity: BDept. of Agriculture, WA Sheep and Biserrula can Control Annual Ryegrass Dean Thomas, John Milton, Mike Ewing and David Lindsay, The University of WA, Clinton Revell, Department of Agriculture, Western Australia Sustainable Management Pasture Utilisation, Fleece Weight and Weaning Rate are Integral to the Profitability of Dohnes and SAMMs. Emma Kopke,Department of Agriculture Western Australia, John Young, Farming Systems Analysis Service Environmental Impact of Sheep Confinement Feeding Systems E A Dowling and E K Crossley, Department of Agriculture, Western Australia Smart Grazing Management for Production and Environmental Outcomes Dr Brien E (Ben) Norton, Centre for the Management of Arid Environments, Curtin University of Technology, WA Common Causes of Plant Poisoning in the Eastern Wheatbelt of Western Australia. Roy Butler, Department of Agriculture, Western Australia Selecting Sheep for Resistance to Worms and Production Trait Responses John Karlsson, Johan Greeff, Department of Agriculture, Western Australia, Geoff Pollott, Imperial College, London UK Production and Water Use of Lucerne and French Serradella in Four Soil Types, Diana Fedorenko1,4, Darryl McClements2,4 and Robert Beard3,4, 12Department of Agriculture, Western Australia; 3Farmer, Meckering; 4CRC for Plant-based Management of Dryland Salinity. Worm Burdens in Sheep at Slaughter Brown Besier, Department of Agriculture Western Australia, Una Ryan, Caroline Bath, Murdoch Universit

Planck 2013 results. XXII. Constraints on inflation

We analyse the implications of the Planck data for cosmic inflation. The Planck nominal mission temperature anisotropy measurements, combined with the WMAP large-angle polarization, constrain the scalar spectral index to be ns = 0:9603 _ 0:0073, ruling out exact scale invariance at over 5_: Planck establishes an upper bound on the tensor-to-scalar ratio of r < 0:11 (95% CL). The Planck data thus shrink the space of allowed standard inflationary models, preferring potentials with V00 < 0. Exponential potential models, the simplest hybrid inflationary models, and monomial potential models of degree n _ 2 do not provide a good fit to the data. Planck does not find statistically significant running of the scalar spectral index, obtaining dns=dln k = 0:0134 _ 0:0090. We verify these conclusions through a numerical analysis, which makes no slowroll approximation, and carry out a Bayesian parameter estimation and model-selection analysis for a number of inflationary models including monomial, natural, and hilltop potentials. For each model, we present the Planck constraints on the parameters of the potential and explore several possibilities for the post-inflationary entropy generation epoch, thus obtaining nontrivial data-driven constraints. We also present a direct reconstruction of the observable range of the inflaton potential. Unless a quartic term is allowed in the potential, we find results consistent with second-order slow-roll predictions. We also investigate whether the primordial power spectrum contains any features. We find that models with a parameterized oscillatory feature improve the fit by __2 e_ _ 10; however, Bayesian evidence does not prefer these models. We constrain several single-field inflation models with generalized Lagrangians by combining power spectrum data with Planck bounds on fNL. Planck constrains with unprecedented accuracy the amplitude and possible correlation (with the adiabatic mode) of non-decaying isocurvature fluctuations. The fractional primordial contributions of cold dark matter (CDM) isocurvature modes of the types expected in the curvaton and axion scenarios have upper bounds of 0.25% and 3.9% (95% CL), respectively. In models with arbitrarily correlated CDM or neutrino isocurvature modes, an anticorrelated isocurvature component can improve the _2 e_ by approximately 4 as a result of slightly lowering the theoretical prediction for the ` <_ 40 multipoles relative to the higher multipoles. Nonetheless, the data are consistent with adiabatic initial conditions

Ecological influences on the behaviour and fertility of malaria parasites

BACKGROUND: Sexual reproduction in the mosquito is essential for the transmission of malaria parasites and a major target for transmission-blocking interventions. Male gametes need to locate and fertilize females in the challenging environment of the mosquito blood meal, but remarkably little is known about the ecology and behaviour of male gametes. METHODS: Here, a series of experiments explores how some aspects of the chemical and physical environment experienced during mating impacts upon the production, motility, and fertility of male gametes. RESULTS AND CONCLUSIONS: Specifically, the data confirm that: (a) rates of male gametogenesis vary when induced by the family of compounds (tryptophan metabolites) thought to trigger gamete differentiation in nature; and (b) complex relationships between gametogenesis and mating success exist across parasite species. In addition, the data reveal that (c) microparticles of the same size as red blood cells negatively affect mating success; and (d) instead of swimming in random directions, male gametes may be attracted by female gametes. Understanding the mating ecology of malaria parasites, may offer novel approaches for blocking transmission and explain adaptation to different species of mosquito vectors

A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen-presenting cells via LILRB1

In healthy individuals, the non-classical MHC molecule HLA-G is only expressed on fetal trophoblast cells that invade the decidua during placentation. We show that a significant proportion of HLA-G at the surface of normal human trophoblast cells is present as a disulphide-linked homodimer of the conventional β2m-associated HLA-I complex. HLA-G is a ligand for leukocyte immunoglobulin-like receptors (LILR), which bind much more efficiently to dimeric HLA-G than to conventional HLA-I molecules. We find that a LILRB1-Fc fusion protein preferentially binds the dimeric form of HLA-G on trophoblast cells. We detect LILRB1 expression on decidual myelomonocytic cells; therefore, trophoblast HLA-G may modulate the function of these cells. Co-culture with HLA-G+ cells does not inhibit monocyte-derived dendritic cell up-regulation of HLA-DR and costimulatory molecules on maturation, but did increase production of IL-6 and IL-10. Furthermore, proliferation of allogeneic lymphocytes was inhibited by HLA-G binding to LILRB1/2 on responding antigen-presenting cells (APC). As HLA-G is the only HLA-I molecule that forms β2m-associated dimers with increased avidity for LILRB1, this interaction could represent a placental-specific signal to decidual APC. We suggest that the placenta is modulating maternal immune responses locally in the uterus through HLA-G, a trophoblast-specific, monomorphic signal present in almost every pregnancy

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre