Pliocene and Eocene provide best analogs for near-future climates.

As the world warms due to rising greenhouse gas concentrations, the Earth system moves toward climate states without societal precedent, challenging adaptation. Past Earth system states offer possible model systems for the warming world of the coming decades. These include the climate states of the Early Eocene (ca. 50 Ma), the Mid-Pliocene (3.3-3.0 Ma), the Last Interglacial (129-116 ka), the Mid-Holocene (6 ka), preindustrial (ca. 1850 CE), and the 20th century. Here, we quantitatively assess the similarity of future projected climate states to these six geohistorical benchmarks using simulations from the Hadley Centre Coupled Model Version 3 (HadCM3), the Goddard Institute for Space Studies Model E2-R (GISS), and the Community Climate System Model, Versions 3 and 4 (CCSM) Earth system models. Under the Representative Concentration Pathway 8.5 (RCP8.5) emission scenario, by 2030 CE, future climates most closely resemble Mid-Pliocene climates, and by 2150 CE, they most closely resemble Eocene climates. Under RCP4.5, climate stabilizes at Pliocene-like conditions by 2040 CE. Pliocene-like and Eocene-like climates emerge first in continental interiors and then expand outward. Geologically novel climates are uncommon in RCP4.5 (<1%) but reach 8.7% of the globe under RCP8.5, characterized by high temperatures and precipitation. Hence, RCP4.5 is roughly equivalent to stabilizing at Pliocene-like climates, while unmitigated emission trajectories, such as RCP8.5, are similar to reversing millions of years of long-term cooling on the scale of a few human generations. Both the emergence of geologically novel climates and the rapid reversion to Eocene-like climates may be outside the range of evolutionary adaptive capacity.

Autoantibodies to islet antigen-2 are associated with HLA-DRB1*07 and DRB1*09 haplotypes as well as DRB1*04 at onset of type 1 diabetes: the possible role of HLA-DQA in autoimmunity to IA-2.

AIMS/HYPOTHESIS: To further our understanding of antigen presentation by HLA class II molecules, we have examined the influence of HLA class II genotype on expression of autoantibodies to islet antigen-2 (IA-2A). METHODS: HLA class II genotype and IA-2A were determined within 3 months of diagnosis in 618 patients with type 1 diabetes (median age 11 years [range 0.7-20.9]). Antibodies to the juxtamembrane region of IA-2 were measured by a radiobinding assay in 481 of 484 IA-2A-positive patients. RESULTS: IA-2A prevalence was highest in patients carrying at least one HLA-DRB1*04-DQA1*0301 (385 of 450; 86%), DRB1*07-DQA1*(0201 or 0301) (58 of 64; 91%) or DRB1*09-DQA1*0301 haplotype (18 of 19; 95%). Multiple regression showed that IA-2A were strongly associated with the number of these haplotypes carried; only 69 of 132 (52%) patients carrying none of these haplotypes had IA-2A, compared with 322 of 391 (82%) patients with one and 93 of 95 (98%) with two of these haplotypes (p < 0.001). IA-2 juxtamembrane antibodies were less frequent in IA-2A-positive patients with one (35%) or two (36%) DRB1*03-DQB1*02 or DRB1*07-DQB1*02 haplotypes than in those negative for these haplotypes (52%) (p = 0.002), but showed an independent positive association with IA-2A level (p < 0.001). CONCLUSIONS/INTERPRETATION: HLA class II alleles strongly influence the prevalence of IA-2A. The high IA-2A prevalence in patients carrying DRB1*04, DRB1*07 and DRB1*09 alleles in linkage disequilibrium with DQA1*0301 or the closely related DQA1*0201 suggests the humoral response to IA-2 may be driven by HLA-DQA1 genes.

Process in psychotherapy as decreasing asymmetry between patient and therapist: evidence from the verbal interaction.

Transcripts of over half the sessions of a psychodynamically oriented psychotherapy were coded to show amount of speech by patient and therapist, and role dimensions derived from Stiles' Verbal Response Mode system. Results indicate the process of psychotherapy as one of decreasing asymmetry between participants, in both activity and status.