We assessed gene expression profiles in 2,752 twins, using a classic twin design to quantify expression heritability and quantitative trait loci (eQTL) in peripheral blood. The most highly heritable genes (~777) were grouped into distinct expression clusters, enriched in gene-poor regions, associated with specific gene function/ontology classes, and strongly associated with disease designation. The design enabled a comparison of twin-based heritability to estimates based on dizygotic IBD sharing and distant genetic relatedness. Consideration of sampling variation suggests that previous heritability estimates have been upwardly biased. Genotyping of 2,494 twins enabled powerful identification of eQTLs, which were further examined in a replication set of 1,895 unrelated subjects. A large number of local eQTLs (6,988) met replication criteria, while a relatively small number of distant eQTLs (165) met quality control and replication standards. Our results provide an important new resource toward understanding the genetic control of transcription.

ObjectivesTo investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure.MethodsThis 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24.ResultsThe primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was −1.0 and −0.94 with FIL200+MTX and FIL100+MTX, respectively, versus −0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments.ConclusionsFIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.

Abstract. Atmospheric pollution has become a serious environmental and social problem in China. Over the past 30 years, the number of winter (December–February) haze days over the North China Plain (WHDNCP) was greatest in 2014. In addition to anthropogenic influence, climate anomalies also played a role. Thus, it is necessary to analyze the anomalous atmosphere circulations associated with haze pollution of this year in detail. Near the surface, the weaker East Asian winter monsoon pattern, causing southerly winds over the North China Plain, could aggravate the situation of haze. In the lower and middle troposphere, taking the anticyclone circulation over North China as an intermediate system, the positive phases of the eastern Atlantic/western Russia (EA/WR), the western Pacific (WP), and the Eurasia (EU) patterns led to a worse air pollution dispersion condition that contributed to a larger number of WHDNCP. In 2014, these three patterns could be recognized from the wind anomalies in the lower troposphere. The preceding autumn (September–November) Arctic sea ice (ASI) anomalies over the eastern Hemisphere and the warmer winter surface over Eurasia might have induced or intensified the positive EA/WR pattern in 2014. These two external forcings, together with the pre-autumn sea surface temperature anomalies in the Pacific, might have also stimulated or enhanced the positive EU-like patterns. The anomalous surface temperature in autumn 2014 was efficient in intensifying anomalous circulations such as the positive phase of the WP pattern. The opposite case of minimum WHDNCP in 2010 further supports the mechanism of how EA/WR and WP patterns and associated external factors altered the local climate conditions to impact the WHDNCP.

Abstract. In the east of China, recent haze pollution has been severe and damaging. In addition to anthropogenic emissions, atmospheric circulations and local meteorological conditions were conducive factors. The number of December haze days over North China and the Huanghuai area has increased sharply since 2010 and was greatest in 2016. During 2016, the most aggressive control measures for anthropogenic emissions were implemented from 16 to 21 December, but the most severe haze pollution still occurred, covering approximately 25 % of the land area of China and lasting for 6 days. The atmospheric circulations must play critical roles in the sub-seasonal haze events. Actually, the positive phase of the East Atlantic-West Russia pattern in the middle troposphere strengthened the anomalous anti-cyclone over the NH area that confined vertical motion below. The associated southerly anomalies made the cold air and surface wind speed weaker, but enhanced the humid flow. Thus, the horizontal and vertical dispersion of atmospheric particulates was suppressed and the pollutants gathered within a narrow space. In December 2016, these key indices were strongly beneficial for haze occurrence and combined to result in the severest haze pollution. The influences of the preceding autumn sea surface temperature near the Gulf of Alaska and the subtropical eastern Pacific, October-November snow cover in western Siberia, and associated physical processes on haze pollution are also discussed.