Lower edge of locked Main Himalayan Thrust unzipped by the 2015 Gorkha earthquake

Large earthquakes are thought to release strain on previously locked faults. However, the details of how earthquakes are initiated, grow and terminate in relation to pre-seismically locked and creeping patches is unclear ^1-4. The 2015 Mw 7.8 Gorkha, Nepal earthquake occurred close to Kathmandu in a region where the prior pattern of fault locking is well documented ^5. Here we analyze this event using seismological records measured at teleseismic distances and Synthetic Aperture Radar imagery. We show that the earthquake originated northwest of Kathmandu within a cluster of background seismicity that fringes the bottom of the locked portion of the Main Himalayan Thrust fault (MHT). The rupture propagated eastwards for about 140 km, unzipping the lower edge of the locked portion of the fault. High-frequency seismic waves radiated continuously as the slip pulse propagated at about 2.8 km s-1 along this zone of presumably high and heterogeneous pre-¬seismic stress at the seismic-aseismic transition. Eastward unzipping of the fault resumed during the Mw 7.3 aftershock on May 12. The transfer of stress to neighbouring regions during the Gorkha earthquake should facilitate future rupture of the areas of the MHT adjacent and up-dip of the Gorkha earthquake rupture.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ngeo251

CD6 and Syntaxin Binding Protein 6 Variants and Response to Tumor Necrosis Factor Alpha Inhibitors in Danish Patients with Rheumatoid Arthritis

<div><h3>Background</h3><p>TNFα inhibitor therapy has greatly improved the treatment of patients with rheumatoid arthritis, however at least 30% do not respond. We aimed to investigate insertions and deletions (INDELS) associated with response to TNFα inhibitors in patients with rheumatoid arthritis (RA).</p> <h3>Methodology and Principal Findings</h3><p>In the DANBIO Registry we identified 237 TNFα inhibitor naïve patients with RA (81% women; median age 56 years; disease duration 6 years) who initiated treatment with infliximab (n = 160), adalimumab (n = 56) or etanercept (n = 21) between 1999 and 2008 according to national treatment guidelines. Clinical response was assessed at week 26 using EULAR response criteria. Based on literature, we selected 213 INDELS potentially related to RA and treatment response using the GeneVa® (Compugen) <em>in silico</em> database of 350,000 genetic variations in the human genome. Genomic segments were amplified by polymerase chain reaction (PCR), and genotyped by Sanger sequencing or fragment analysis. We tested the association between genotypes and EULAR good response versus no response, and EULAR good response versus moderate/no response using Fisher’s exact test. At baseline the median DAS28 was 5.1. At week 26, 68 (29%) patients were EULAR good responders, while 81 (34%) and 88 (37%) patients were moderate and non-responders, respectively. A 19 base pair insertion within the CD6 gene was associated with EULAR good response vs. no response (OR = 4.43, 95% CI: 1.99–10.09, p = 7.211×10⁻⁵) and with EULAR good response vs. moderate/no response (OR = 4.54, 95% CI: 2.29–8.99, p = 3.336×10⁻⁶). A microsatellite within the syntaxin binding protein 6 (STXBP6) was associated with EULAR good response vs. no response (OR = 4.01, 95% CI: 1.92–8.49, p = 5.067×10⁻⁵).</p> <h3>Conclusion</h3><p>Genetic variations within CD6 and STXBP6 may influence response to TNFα inhibitors in patients with RA.</p> </div

Overestimation of the earthquake hazard along the Himalaya: constraints in bracketing of medieval earthquakes from paleoseismic studies

Abstract The Himalaya is one of the most seismically active regions of the world. The occurrence of several large magnitude earthquakes viz. 1905 Kangra earthquake (Mw 7.8), 1934 Bihar–Nepal earthquake (Mw 8.2), 1950 Assam earthquake (Mw 8.4), 2005 Kashmir (Mw 7.6), and 2015 Gorkha (Mw 7.8) are the testimony to ongoing tectonic activity. In the last few decades, tremendous efforts have been made along the Himalayan arc to understand the patterns of earthquake occurrences, size, extent, and return periods. Some of the large magnitude earthquakes produced surface rupture, while some remained blind. Furthermore, due to the incompleteness of the earthquake catalogue, a very few events can be correlated with medieval earthquakes. Based on the existing paleoseismic data certainly, there exists a complexity to precisely determine the extent of surface rupture of these earthquakes and also for those events, which occurred during historic times. In this paper, we have compiled the paleo-seismological data and recalibrated the radiocarbon ages from the trenches excavated by previous workers along the entire Himalaya and compared earthquake scenario with the past. Our studies suggest that there were multiple earthquake events with overlapping surface ruptures in small patches with an average rupture length of ~300 km limiting Mw 7.8–8.0 for the Himalayan arc, rather than two or three giant earthquakes rupturing the whole front. It has been identified that the large magnitude Himalayan earthquakes, such as 1905 Kangra, 1934 Bihar–Nepal, and 1950 Assam, that have occurred within a time frame of 45 years. Now, if these events are dated, there is a high possibility that within the range of ±50 years, they may be considered as the remnant of one giant earthquake rupturing the entire Himalayan arc. Therefore, leading to an overestimation of seismic hazard scenario in Himalaya