Explore the vast range of titles available.

Objectives To determine the quantitative efficacy of different classes of blood pressure lowering drugs in preventing coronary heart disease (CHD) and stroke, and who should receive treatment.Design Meta-analysis.Data source Medline (1966-2007).Study selection Randomised trials of blood pressure lowering drugs recording CHD events and strokes. 108 trials studied differences in blood pressure between study drug and placebo (or control group not receiving the study drug) (“blood pressure difference trials”), and 46 trials compared drugs (“drug comparison trials”). Seven trials with three randomised groups fell into both categories. The results were interpreted in the context of those expected from the largest published meta-analysis of cohort studies, totalling 958 000 people.Participants 464 000 people defined into three mutually exclusive categories: participants with no history of vascular disease, a history of CHD, or a history of stroke.Results In the blood pressure difference trials β blockers had a special effect over and above that due to blood pressure reduction in preventing recurrent CHD events in people with a history of CHD: risk reduction 29% (95% confidence interval 22% to 34%) compared with 15% (11% to 19%) in trials of other drugs. The extra effect was limited to a few years after myocardial infarction, with a risk reduction of 31% compared with 13% in people with CHD with no recent infarct (P=0.04). In the other blood pressure difference trials (excluding CHD events in trials of β blockers in people with CHD), there was a 22% reduction in CHD events (17% to 27%) and a 41% (33% to 48%) reduction in stroke for a blood pressure reduction of 10 mm Hg systolic or 5 mm Hg diastolic, similar to the reductions of 25% (CHD) and 36% (stroke) expected for the same difference in blood pressure from the cohort study meta-analysis, indicating that the benefit is explained by blood pressure reduction itself. The five main classes of blood pressure lowering drugs (thiazides, β blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers) were similarly effective (within a few percentage points) in preventing CHD events and strokes, with the exception that calcium channel blockers had a greater preventive effect on stroke (relative risk 0.92, 95% confidence interval 0.85 to 0.98). The percentage reductions in CHD events and stroke were similar in people with and without cardiovascular disease and regardless of blood pressure before treatment (down to 110 mm Hg systolic and 70 mm Hg diastolic). Combining our results with those from two other studies (the meta-analyses of blood pressure cohort studies and of trials determining the blood pressure lowering effects of drugs according to dose) showed that in people aged 60-69 with a diastolic blood pressure before treatment of 90 mm Hg, three drugs at half standard dose in combination reduced the risk of CHD by an estimated 46% and of stroke by 62%; one drug at standard dose had about half this effect. The present meta-analysis also showed that drugs other than calcium channel blockers (with the exception of non-cardioselective β blockers) reduced the incidence of heart failure by 24% (19% to 28%) and calcium channel blockers by 19% (6% to 31%).Conclusions With the exception of the extra protective effect of β blockers given shortly after a myocardial infarction and the minor additional effect of calcium channel blockers in preventing stroke, all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure so excluding material pleiotropic effects. The proportional reduction in cardiovascular disease events was the same or similar regardless of pretreatment blood pressure and the presence or absence of existing cardiovascular disease. Guidelines on the use of blood pressure lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure. Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some.

Carbon storage by many terrestrial ecosystems can be limited by nutrients, predominantly nitrogen (N) and phosphorus (P), in addition to other environmental constraints, water, light and temperature. However the spatial distribution and the extent of both N and P limitation at the global scale have not been quantified. Here we have developed a global model of carbon (C), nitrogen (N) and phosphorus (P) cycles for the terrestrial biosphere. Model estimates of steady state C and N pool sizes and major fluxes between plant, litter and soil pools, under present climate conditions, agree well with various independent estimates. The total amount of C in the terrestrial biosphere is 2767 Gt C, and the C fractions in plant, litter and soil organic matter are 19%, 4% and 77%. The total amount of N is 135 Gt N, with about 94% stored in the soil, 5% in the plant live biomass, and 1% in litter. We found that the estimates of total soil P and its partitioning into different pools in soil are quite sensitive to biochemical P mineralization. The total amount of P (plant biomass, litter and soil) excluding occluded P in soil is 17 Gt P in the terrestrial biosphere, 33% of which is stored in the soil organic matter if biochemical P mineralization is modelled, or 31 Gt P with 67% in soil organic matter otherwise. This model was used to derive the global distribution and uncertainty of N or P limitation on the productivity of terrestrial ecosystems at steady state under present conditions. Our model estimates that the net primary productivity of most tropical evergreen broadleaf forests and tropical savannahs is reduced by about 20% on average by P limitation, and most of the remaining biomes are N limited; N limitation is strongest in high latitude deciduous needle leaf forests, and reduces its net primary productivity by up to 40% under present conditions.

Abstract Objectives To determine by how much statins reduce serum concentrations of low density lipoprotein (LDL) cholesterol and incidence of ischaemic heart disease (IHD) events and stroke, according to drug, dose, and duration of treatment. Design Three meta-analyses: 164 short term randomised placebo controlled trials of six statins and LDL cholesterol reduction; 58 randomised trials of cholesterol lowering by any means and IHD events; and nine cohort studies and the same 58 trials on stoke. Main outcome measures Reductions in LDL cholesterol according to statin and dose; reduction in IHD events and stroke for a specified reduction in LDL cholesterol. Results Reductions in LDL cholesterol (in the 164 trials) were 2.8 mmol/l (60%) with rosuvastatin 80 mg/day, 2.6 mmol/l (55%) with atorvastatin 80 mg/day, 1.8 mmol/l (40%) with atorvastatin 10 mg/day, lovastatin 40 mg/day, simvastatin 40 mg/day, or rosuvastatin 5 mg/day, all from pretreatment concentrations of 4.8 mmol/l. Pravastatin and fluvastatin achieved smaller reductions. In the 58 trials, for an LDL cholesterol reduction of 1.0 mmol/l the risk of IHD events was reduced by 11% in the first year of treatment, 24% in the second year, 33% in years three to five, and by 36% thereafter (P < 0.001 for trend). IHD events were reduced by 20%, 31%, and 51% in trials grouped by LDL cholesterol reduction (means 0.5 mmol/l, 1.0 mmol/l, and 1.6 mmol/l) after results from first two years of treatment were excluded (P < 0.001 for trend). After several years a reduction of 1.8 mmol/l would reduce IHD events by an estimated 61%. Results from the same 58 trials, corroborated by results from the nine cohort studies, show that lowering LDL cholesterol decreases all stroke by 10% for a 1 mmol/l reduction and 17% for a 1.8 mmol/l reduction. Estimates allow for the fact that trials tended to recruit people with vascular disease, among whom the effect of LDL cholesterol reduction on stroke is greater because of their higher risk of thromboembolic stroke (rather than haemorrhagic stroke) compared with people in the general population. Conclusions Statins can lower LDL cholesterol concentration by an average of 1.8 mmol/l which reduces the risk of IHD events by about 60% and stroke by 17%.

Increasing atmospheric carbon dioxide (CO 2 ) is the principal driver of anthropogenic climate change. Asia is an important region for the global carbon budget, with 4 of the world’s 10 largest national emitters of CO 2 . Using an ensemble of seven atmospheric inverse systems, we estimated land biosphere fluxes (natural, land-use change and fires) based on atmospheric observations of CO 2 concentration. The Asian land biosphere was a net sink of −0.46 (−0.70–0.24) PgC per year (median and range) for 1996–2012 and was mostly located in East Asia, while in South and Southeast Asia the land biosphere was close to carbon neutral. In East Asia, the annual CO 2 sink increased between 1996–2001 and 2008–2012 by 0.56 (0.30–0.81) PgC, accounting for ∼35% of the increase in the global land biosphere sink. Uncertainty in the fossil fuel emissions contributes significantly (32%) to the uncertainty in land biosphere sink change. Land biosphere uptake of carbon is important in mitigating the anthropogenic increase in atmospheric CO 2 and its climate forcing. Here, the authors show that land biosphere uptake of carbon in Asia has increased substantially since the mid 1990s, likely owing to reforestation and regional climate change.

The Southern Ocean (44-75° S) plays a critical role in the global carbon cycle, yet remains one of the most poorly sampled ocean regions. Different approaches have been used to estimate sea-air CO2 fluxes in this region: synthesis of surface ocean observations, ocean biogeochemical models, and atmospheric and ocean inversions. As part of the RECCAP (REgional Carbon Cycle Assessment and Processes) project, we combine these different approaches to quantify and assess the magnitude and variability in Southern Ocean sea-air CO2 fluxes between 1990-2009. Using all models and inversions (26), the integrated median annual sea-air CO2 flux of -0.42 ± 0.07 Pg C yr-1 for the 44-75° S region, is consistent with the -0.27 ± 0.13 Pg C yr-1 calculated using surface observations. The circumpolar region south of 58° S has a small net annual flux (model and inversion median: -0.04 ± 0.07 Pg C yr-1 and observations: +0.04 ± 0.02 Pg C yr-1 ), with most of the net annual flux located in the 44 to 58° S circumpolar band (model and inversion median: -0.36 ± 0.09 Pg C yr-1 and observations: -0.35 ± 0.09 Pg C yr-1 ). Seasonally, in the 44-58° S region, the median of 5 ocean biogeochemical models captures the observed sea-air CO2 flux seasonal cycle, while the median of 11 atmospheric inversions shows little seasonal change in the net flux. South of 58° S, neither atmospheric inversions nor ocean biogeochemical models reproduce the phase and amplitude of the observed seasonal sea-air CO2 flux, particularly in the Austral Winter. Importantly, no individual atmospheric inversion or ocean biogeochemical model is capable of reproducing both the observed annual mean uptake and the observed seasonal cycle. This raises concerns about projecting future changes in Southern Ocean CO2 fluxes. The median interannual variability from atmospheric inversions and ocean biogeochemical models is substantial in the Southern Ocean; up to 25% of the annual mean flux, with 25% of this interannual variability attributed to the region south of 58° S. Resolving long-term trends is difficult due to the large interannual variability and short time frame (1990-2009) of this study; this is particularly evident from the large spread in trends from inversions and ocean biogeochemical models. Nevertheless, in the period 1990-2009 ocean biogeochemical models do show increasing oceanic uptake consistent with the expected increase of -0.05 Pg C yr-1 decade-1 . In contrast, atmospheric inversions suggest little change in the strength of the CO2 sink broadly consistent with the results of Le Quéré et al. (2007).

Atmospheric CO2 inversions estimate surface carbon fluxes from an optimal fit to atmospheric CO2 measurements, usually including prior constraints on the flux estimates. Eleven sets of carbon flux estimates are compared, generated by different inversions systems that vary in their inversions methods, choice of atmospheric data, transport model and prior information. The inversions were run for at least 5 yr in the period between 1990 and 2010. Mean fluxes for 2001-2004, seasonal cycles, interannual variability and trends are compared for the tropics and northern and southern extra-tropics, and separately for land and ocean. Some continental/basin-scale subdivisions are also considered where the atmospheric network is denser. Four-year mean fluxes are reasonably consistent across inversions at global/latitudinal scale, with a large total (land plus ocean) carbon uptake in the north (-3.4 Pg C yr-1 (±0.5 Pg C yr-1 standard deviation), with slightly more uptake over land than over ocean), a significant although more variable source over the tropics (1.6 ± 0.9 Pg C yr-1 ) and a compensatory sink of similar magnitude in the south (-1.4 ± 0.5 Pg C yr-1 ) corresponding mainly to an ocean sink. Largest differences across inversions occur in the balance between tropical land sources and southern land sinks. Interannual variability (IAV) in carbon fluxes is larger for land than ocean regions (standard deviation around 1.06 versus 0.33 Pg C yr-1 for the 1996-2007 period), with much higher consistency among the inversions for the land. While the tropical land explains most of the IAV (standard deviation ~ 0.65 Pg C yr-1 ), the northern and southern land also contribute (standard deviation ~ 0.39 Pg C yr-1 ). Most inversions tend to indicate an increase of the northern land carbon uptake from late 1990s to 2008 (around 0.1 Pg C yr-1 , predominantly in North Asia. The mean seasonal cycle appears to be well constrained by the atmospheric data over the northern land (at the continental scale), but still highly dependent on the prior flux seasonality over the ocean. Finally we provide recommendations to interpret the regional fluxes, along with the uncertainty estimates.

The scientific understanding of the Earth's climate system, including the central question of how the climate system is likely to respond to human-induced perturbations, is comprehensively captured in GCMs and Earth System Models (ESM). Diagnosing the simulated climate response, and comparing responses across different models, is crucially dependent on transparent assumptions of how the GCM/ESM has been driven - especially because the implementation can involve subjective decisions and may differ between modelling groups performing the same experiment. This paper outlines the climate forcings and setup of the Met Office Hadley Centre ESM, HadGEM2-ES for the CMIP5 set of centennial experiments. We document the prescribed greenhouse gas concentrations, aerosol precursors, stratospheric and tropospheric ozone assumptions, as well as implementation of land-use change and natural forcings for the HadGEM2-ES historical and future experiments following the Representative Concentration Pathways. In addition, we provide details of how HadGEM2-ES ensemble members were initialised from the control run and how the palaeoclimate and AMIP experiments, as well as the \"emission-driven\" RCP experiments were performed.

Abstract Objectives To determine the combination of drugs and vitamins, and their doses, for use in a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects. The strategy was to simultaneously reduce four cardiovascular risk factors (low density lipoprotein cholesterol, blood pressure, serum homocysteine, and platelet function) regardless of pretreatment levels. Design We quantified the efficacy and adverse effects of the proposed formulation from published meta-analyses of randomised trials and cohort studies and a meta-analysis of 15 trials of low dose (50-125 mg/day) aspirin. Outcome measures Proportional reduction in ischaemic heart disease (IHD) events and strokes; life years gained; and prevalence of adverse effects. Results The formulation which met our objectives was: a statin (for example, atorvastatin (daily dose 10 mg) or simvastatin (40 mg)); three blood pressure lowering drugs (for example, a thiazide, a β blocker, and an angiotensin converting enzyme inhibitor), each at half standard dose; folic acid (0.8 mg); and aspirin (75 mg). We estimate that the combination (which we call the Polypill) reduces IHD events by 88% (95% confidence interval 84% to 91%) and stroke by 80% (71% to 87%). One third of people taking this pill from age 55 would benefit, gaining on average about 11 years of life free from an IHD event or stroke. Summing the adverse effects of the components observed in randomised trials shows that the Polypill would cause symptoms in 8-15% of people (depending on the precise formulation). Conclusion The Polypill strategy could largely prevent heart attacks and stroke if taken by everyone aged 55 and older and everyone with existing cardiovascular disease. It would be acceptably safe and with widespread use would have a greater impact on the prevention of disease in the Western world than any other single intervention.

A chemistry-transport model (CTM) intercomparison experiment (TransCom-CH4 ) has been designed to investigate the roles of surface emissions, transport and chemical loss in simulating the global methane distribution. Model simulations were conducted using twelve models and four model variants and results were archived for the period of 1990-2007. All but one model transports were driven by reanalysis products from 3 different meteorological agencies. The transport and removal of CH4 in six different emission scenarios were simulated, with net global emissions of 513 ± 9 and 514 ± 14 Tg CH4 yr-1 for the 1990s and 2000s, respectively. Additionally, sulfur hexafluoride (SF6 ) was simulated to check the interhemispheric transport, radon (222 Rn) to check the subgrid scale transport, and methyl chloroform (CH3 CCl3 ) to check the chemical removal by the tropospheric hydroxyl radical (OH). The results are compared to monthly or annual mean time series of CH4 , SF6 and CH3 CCl3 measurements from 8 selected background sites, and to satellite observations of CH4 in the upper troposphere and stratosphere. Most models adequately capture the vertical gradients in the stratosphere, the average long-term trends, seasonal cycles, interannual variations (IAVs) and interhemispheric (IH) gradients at the surface sites for SF6 , CH3 CCl3 and CH4 . The vertical gradients of all tracers between the surface and the upper troposphere are consistent within the models, revealing vertical transport differences between models. An average IH exchange time of 1.39 ± 0.18 yr is derived from SF6 time series. Sensitivity simulations suggest that the estimated trends in exchange time, over the period of 1996-2007, are caused by a change of SF6 emissions towards the tropics. Using six sets of emission scenarios, we show that the decadal average CH4 growth rate likely reached equilibrium in the early 2000s due to the flattening of anthropogenic emission growth since the late 1990s. Up to 60% of the IAVs in the observed CH4 concentrations can be explained by accounting for the IAVs in emissions, from biomass burning and wetlands, as well as meteorology in the forward models. The modeled CH4 budget is shown to depend strongly on the troposphere-stratosphere exchange rate and thus on the model's vertical grid structure and circulation in the lower stratosphere. The 15-model median CH4 and CH3 CCl3 atmospheric lifetimes are estimated to be 9.99 ± 0.08 and 4.61 ± 0.13 yr, respectively, with little IAV due to transport and temperature.

This paper reports a study of the full carbon (C-CO2) budget of the Australian continent, focussing on 1990–2011 in the context of estimates over two centuries. The work is a contribution to the RECCAP (REgional Carbon Cycle Assessment and Processes) project, as one of numerous regional studies. In constructing the budget, we estimate the following component carbon fluxes: net primary production (NPP); net ecosystem production (NEP); fire; land use change (LUC); riverine export; dust export; harvest (wood, crop and livestock) and fossil fuel emissions (both territorial and non-territorial). Major biospheric fluxes were derived using BIOS2 (Haverd et al., 2012), a fine-spatial-resolution (0.05°) offline modelling environment in which predictions of CABLE (Wang et al., 2011), a sophisticated land surface model with carbon cycle, are constrained by multiple observation types. The mean NEP reveals that climate variability and rising CO2 contributed 12 ± 24 (1σ error on mean) and 68 ± 15 TgC yr−1, respectively. However these gains were partially offset by fire and LUC (along with other minor fluxes), which caused net losses of 26 ± 4 TgC yr−1 and 18 ± 7 TgC yr−1, respectively. The resultant net biome production (NBP) is 36 ± 29 TgC yr−1, in which the largest contributions to uncertainty are NEP, fire and LUC. This NBP offset fossil fuel emissions (95 ± 6 TgC yr−1) by 38 ± 30%. The interannual variability (IAV) in the Australian carbon budget exceeds Australia's total carbon emissions by fossil fuel combustion and is dominated by IAV in NEP. Territorial fossil fuel emissions are significantly smaller than the rapidly growing fossil fuel exports: in 2009–2010, Australia exported 2.5 times more carbon in fossil fuels than it emitted by burning fossil fuels.