The "Great Acceleration" graphs, originally published in 2004 to show socioeconomic and Earth System trends from 1750 to 2000, have now been updated to 2010. In the graphs of socioeconomic trends, where the data permit, the activity of the wealthy (OECD) countries, those countries with emerging economies, and the rest of the world have now been differentiated. The dominant feature of the socioeconomic trends is that the economic activity of the human enterprise continues to grow at a rapid rate. However, the differentiated graphs clearly show that strong equity issues are masked by considering global aggregates only. Most of the population growth since 1950 has been in the non-OECD world but the world's economy (GDP), and hence consumption, is still strongly dominated by the OECD world. The Earth System indicators, in general, continued their long-term, postindustrial rise, although a few, such as atmospheric methane concentration and stratospheric ozone loss, showed a slowing or stabilisation over the past decade. The post-1950 acceleration in the Earth System indicators remains clear. Only beyond the mid-20 th century is there clear evidence for fundamental shifts in the state and functioning of the Earth System that are beyond the range of variability of the Holocene and driven by human activities. Thus, of all the candidates for a start date for the Anthropocene, the beginning of the Great Acceleration is by far the most convincing from an Earth System science perspective.

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This paper develops a methodology for identifying that natural capital-called critical natural capital (CNC)-the maintenance of which is essential for environmental sustainability. By consideration of the characteristics of natural capital, of the environmental functions that these characteristics enable natural capital to perform and of the importance of these functions to humans and the biosphere, it shows how sustainability standards in respect of these environmental functions may be derived. The difference between the current situation and these standards is termed the sustainability gap. The methodology that emerges from bringing these ideas together into a single analytical framework enables policy makers to identify the extent of current unsustainability, the principal causes of it, the elements and processes of natural capital (the CNC) which need to be maintained or restored to close the sustainability gap and the costs of so doing. The framework should therefore be of use in identifying priorities and policies for moving towards environmental sustainability.

Major depressive disorder (MDD) is a prevalent and disabling condition, and many patients do not respond to available treatments. Deep transcranial magnetic stimulation (dTMS) is a new technology allowing non-surgical stimulation of relatively deep brain areas. This is the first double-blind randomized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD. We recruited 212 MDD outpatients, aged 22-68 years, who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode. They were randomly assigned to monotherapy with active or sham dTMS. Twenty sessions of dTMS (18 Hz over the prefrontal cortex) were applied during 4 weeks acutely, and then biweekly for 12 weeks. Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale (HDRS-21) score and response/remission rates at week 5, respectively. dTMS induced a 6.39 point improvement in HDRS-21 scores, while a 3.28 point improvement was observed in the sham group (p50.008), resulting in a 0.76 effect size. Response and remission rates were higher in the dTMS than in the sham group (response: 38.4 vs. 21.4%, p50.013; remission: 32.6 vs. 14.6%, p50.005). These differences between active and sham treatment were stable during the 12-week maintenance phase. dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred. These results suggest that dTMS constitutes a novel intervention in MDD, which is efficacious and safe in patients not responding to antidepressant medications, and whose effect remains stable over 3 months of maintenance treatment.

Viral and host factors influence the rate of HIV-1 disease progression. For HIV-1 to fuse, a CD4+ cell must express a co-receptor that the virus can use. The chemokine receptors CCR5 and CXCR4 are used by R5 and X4 viruses, respectively. Most new infections involve transmission of R5 viruses, but variants can arise later that also use CXCR4 (R5-X4 or X4 viruses). This is associated with an increased rate of CD4+ T-cell loss and poor prognosis. The ability of host cells to support HIV-1 entry also influences progression. The absence of CCR5 in approximately 1% of the Caucasian population, due to homozygosity for a 32-nucleotide deletion in the coding region (delta32-CCR5 allele), very strongly protects against HIV-1 transmission. Heterozygosity for the delta32-CCR5 allele delays progression typically by 2 years. A recent study showed that a conservative substitution (V64I) in the coding region of CCR2 also has a significant impact on disease progression, but not on HIV-1 transmission. This was unexpected, since CCR2 is rarely used as a co-receptor in vitro and the V64I change is in a transmembrane region. Because a subsequent study did not confirm this effect on progression to disease, we analyzed CCR2-V64I using subjects in the Chicago MACS. We show that CCR2-V64I is indeed protective against disease progression and go on to show that the CCR2-V64I allele is in complete linkage disequilibrium with a point mutation in the CCR5 regulatory region.