Epidemiological consequences of household-based antiviral prophylaxis for pandemic influenza

Antiviral treatment offers a fast acting alternative to vaccination; as such it is viewed as a first-line of defence against pandemic influenza in protecting families and households once infection has been detected. In clinical trials, antiviral treatments have been shown to be efficacious in preventing infection, limiting disease and reducing transmission, yet their impact at containing the 2009 influenza A(H1N1)pdm outbreak was limited. To understand this seeming discrepancy, we develop a general and computationally efficient model for studying household-based interventions. This allows us to account for uncertainty in quantities relevant to the 2009 pandemic in a principled way, accounting for the heterogeneity and variability in each epidemiological process modelled. We find that the population-level effects of delayed antiviral treatment and prophylaxis mean that their limited overall impact is quantitatively consistent (at current levels of precision) with their reported clinical efficacy under ideal conditions. Hence, effective control of pandemic influenza with antivirals is critically dependent on early detection and delivery ideally within 24 h.Andrew J. Black, Thomas House, M. J. Keeling and J. V. Ros

Transcription Profiles of Age-at-Maturity-Associated Genes Suggest Cell Fate Commitment Regulation as a Key Factor in the Atlantic Salmon Maturation Process

Despite recent taxonomic diversification in studies linking genotype with phenotype, follow-up studies aimed at understanding the molecular processes of such genotype-phenotype associations remain rare. The age at which an individual reaches sexual maturity is an important fitness trait in many wild species. However, the molecular mechanisms regulating maturation timing processes remain obscure. A recent genome-wide association study in Atlantic salmon (Salmo salar) identified large-effect age-at-maturity-associated chromosomal regions including genes vgll3, akap11 and six6, which have roles in adipogenesis, spermatogenesis and the hypothalamic-pituitary-gonadal (HPG) axis, respectively. Here, we determine expression patterns of these genes during salmon development and their potential molecular partners and pathways. Using Nanostring transcription profiling technology, we show development- and tissue-specific mRNA expression patterns for vgll3, akap11 and six6. Correlated expression levels of vgll3 and akap11, which have adjacent chromosomal location, suggests they may have shared regulation. Further, vgll3 correlating with arhgap6 and yap1, and akap11 with lats1 and yap1 suggests that Vgll3 and Akap11 take part in actin cytoskeleton regulation. Tissue-specific expression results indicate that vgll3 and akap11 paralogs have sex-dependent expression patterns in gonads. Moreover, six6 correlating with slc38a6 and rtn1, and Hippo signaling genes suggests that Six6 could have a broader role in the HPG neuroendrocrine and cell fate commitment regulation, respectively. We conclude that Vgll3, Akap11 and Six6 may influence Atlantic salmon maturation timing via affecting adipogenesis and gametogenesis by regulating cell fate commitment and the HPG axis. These results may help to unravel general molecular mechanisms behind maturation.Peer reviewe

Atlantic salmon (Salmo salar) age at maturity is strongly affected by temperature, population and age-at-maturity genotype

Age at maturity can vary dramatically within some species. We show that, when raised in controlled conditions, Atlantic salmon age at maturity is affected greatly by temperature as well as a recently discovered age-at-maturity gene. The influence of temperature on age at maturity differed between two populations, but the effect of the age-at-maturity gene was similar in both temperatures and populations.Age at maturity is a key life history trait involving a trade-off between survival risk and reproductive investment, and is an important factor for population structures. In ectotherms, a warming environment may have a dramatic influence on development and life history, but this influence may differ between populations. While an increasing number of studies have examined population-dependent reactions with temperature, few have investigated this in the context of maturation timing. Atlantic salmon, a species of high conservation relevance, is a good study species for this topic as it displays considerable variation in age at maturity, of which a large proportion has been associated with a genomic region including the strong candidate gene vgll3. Until now, the effect of this gene in the context of different environments and populations has not been studied. Using a large-scale common-garden experiment, we find strong effects of temperature, population-of-origin, and vgll3 genotype on maturation in 2-year-old male Atlantic salmon (Salmo salar). With a temperature difference of 1.8 degrees C, maturation probability was 4.8 times higher in the warm treatment than the cold treatment. This temperature effect was population-specific and was higher in the southern (60.48 degrees N) compared to the northern (65.01 degrees N) population. The early maturation vgll3*E allele was associated with a significantly higher maturation probability, but there was no vgll3 interaction with temperature or population. Both body condition and body mass associated with maturation. The body mass association was only present in the warm treatment. Our findings demonstrate that (i) populations can vary in their response to temperature change in terms of age at maturity, (ii) high intrinsic growth could be associated with higher thermal sensitivity for life history variation and (iii) vgll3 effects on age at maturity might be similar between populations and different thermal environments.Peer reviewe

Discrete wetland groundwater discharges revealed with a three-dimensional temperature model and botanical indicators (Boxford, UK)

Wetlands provide unique goods and services, as habitats of high biodiversity. Hydrology is the principal control on wetland functioning; hence, understanding the water source is fundamental. However, groundwater inflows may be discrete and easily missed. Research techniques are required with low cost and minimal impact in sensitive settings. In this study, the effectiveness of using a three-dimensional (3D) temperature model and botanical indicators to characterise groundwater discharge is explored at the CEH (Centre for Ecology and Hydrology) River Lambourn Observatory, Boxford, UK. This comprises a 10 ha lowland riparian wetland, designated for its scientific interest and conservation value. Temperature data were collected in winter at multiple depths down to 0.9 m over approximately 3.6 ha and transformed into a 3D model via ordinary kriging. Anomalous warm zones indicated distinct areas of groundwater upwelling which were concurrent with relic channel structures. Lateral heat propagation from the channels was minimal and restricted to within 5–10 m. Vertical temperature sections within the channels suggest varying degrees of groundwater discharge along their length. Hydrochemical analysis showed that warmer peat waters were akin to deeper aquifer waters, confirming the temperature anomalies as areas of groundwater discharge. Subsequently, a targeted vegetation survey identified Carex paniculata as an indicator of groundwater discharge. The upwelling groundwater contains high concentrations of nitrate which is considered to support the spatially restricted growth of Carex paniculata against a background of poor fen communities located in reducing higher-phosphate waters

Inadequacy of cardiovascular risk factor management in chronic kidney transplantation - evidence from the FAVORIT study

Kidney transplant recipients (KTRs) have increased risk for cardiovascular disease (CVD). Our objective is to describe the prevalence of CVD risk factors applying standard criteria and use of CVD risk factor lowering medications in contemporary KTRs

Maturation in Atlantic salmon (Salmo salar, Salmonidae) : a synthesis of ecological, genetic, and molecular processes

Over the past decades, Atlantic salmon (Salmo salar, Salmonidae) has emerged as a model system for sexual maturation research, owing to the high diversity of life history strategies, knowledge of trait genetic architecture, and their high economic value. The aim of this synthesis is to summarize the current state of knowledge concerning maturation in Atlantic salmon, outline knowledge gaps, and provide a roadmap for future work. We summarize the current state of knowledge: 1) maturation in Atlantic salmon takes place over the entire life cycle, starting as early as embryo development, 2) variation in the timing of maturation promotes diversity in life history strategies, 3) ecological and genetic factors influence maturation, 4) maturation processes are sex-specific and may have fitness consequences for each sex, 5) genomic studies have identified large-effect loci that influence maturation, 6) the brain-pituitary-gonadal axis regulates molecular and physiological processes of maturation, 7) maturation is a key component of fisheries, aquaculture, conservation, and management, and 8) climate change, fishing pressure, and other anthropogenic stressors likely have major effects on salmon maturation. In the future, maturation research should focus on a broader diversity of life history stages, including early embryonic development, the marine phase and return migration. We recommend studies combining ecological and genetic approaches will help disentangle the relative contributions of effects in different life history stages to maturation. Functional validation of large-effect loci should reveal how these genes influence maturation. Finally, continued research in maturation will improve our predictions concerning how salmon may adapt to fisheries, climate change, and other future challenges.Peer reviewe

Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort

Mild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality

The ictal wavefront is the spatiotemporal source of discharges during spontaneous human seizures

The extensive distribution and simultaneous termination of seizures across cortical areas has led to the hypothesis that seizures are caused by large-scale coordinated networks spanning these areas. This view, however, is difficult to reconcile with most proposed mechanisms of seizure spread and termination, which operate on a cellular scale. We hypothesize that seizures evolve into self-organized structures wherein a small seizing territory projects high-intensity electrical signals over a broad cortical area. Here we investigate human seizures on both small and large electrophysiological scales. We show that the migrating edge of the seizing territory is the source of travelling waves of synaptic activity into adjacent cortical areas. As the seizure progresses, slow dynamics in induced activity from these waves indicate a weakening and eventual failure of their source. These observations support a parsimonious theory for how large-scale evolution and termination of seizures are driven from a small, migrating cortical area

Regenerative medicine and responsible research and innovation : proposals for a responsible acceleration to the clinic

This paper asks how regenerative medicine can be examined through the ‘responsible research and innovation’ (RRI) approach which has been developed over the past decade. It describes the drivers to the development of RRI, and then argues for the need to understand innovation itself through drawing on social science analysis rooted in science and technology studies. The paper then identifies a number of highly specific challenges faced by the regenerative medicine field and the implications these have for value creation. It offers a number of examples of how a combined RRI/science and technology studies perspective can identify priority areas for policy and concludes by arguing for a ‘responsible acceleration’, more likely to foster readiness at a time when much of the policy domain is pushing for ever-rapid access to cell therapies

Global Carbon Budget 2015

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates as well as consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuels and industry (E-FF) are based on energy statistics and cement production data, while emissions from land-use change (E-LUC), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (G(ATM)) is computed from the annual changes in concentration. The mean ocean CO2 sink (S-OCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in S-OCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (S-LAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO2, and land-cover change (some including nitrogen-carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as +/- 1 sigma, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (20052014), E-FF was 9.0 +/- 0.5 GtC yr(-1) E-LUC was 0.9 +/- 0.5 GtC yr(-1), GATM was 4.4 +/- 0.1 GtC yr(-1), S-OCEAN was 2.6 +/- 0.5 GtC yr(-1), and S LAND was 3.0 +/- 0.8 GtC yr(-1). For the year 2014 alone, E FF grew to 9.8 +/- 0.5 GtC yr(-1), 0.6% above 2013, continuing the growth trend in these emissions, albeit at a slower rate compared to the average growth of 2.2% yr(-1) that took place during 2005-2014. Also, for 2014, E-LUC was 1.1 +/- 0.5 GtC yr(-1), G(ATM) was 3.9 +/- 0.2 GtC yr(-1), S-OCEAN was 2.9 +/- 0.5 GtC yr(-1), and S-LAND was 4.1 +/- 0.9 GtC yr(-1). G(ATM) was lower in 2014 compared to the past decade (2005-2014), reflecting a larger S-LAND for that year. The global atmospheric CO2 concentration reached 397.15 +/- 0.10 ppm averaged over 2014. For 2015, preliminary data indicate that the growth in E-FF will be near or slightly below zero, with a projection of 0.6 [ range of 1.6 to C 0.5] %, based on national emissions projections for China and the USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the global economy for the rest of the world. From this projection of E-FF and assumed constant E LUC for 2015, cumulative emissions of CO2 will reach about 555 +/- 55 GtC (2035 +/- 205 GtCO(2)) for 1870-2015, about 75% from E FF and 25% from E LUC. This living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quere et al., 2015, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi: 10.3334/CDIAC/GCP_2015)