Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus

Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33×10−11, OR = 1.29; WDFY4: rs7097397, P = 8.15×10−12, OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3′-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved

Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Effects of soil density on grass-induced suction distributions in compacted soil subjected to rainfall

Grass is recognized as being beneficial in reducing rainfall infiltration in some kinds of surface cover systems such as landfill cover, because rainwater discharges as surface runoff due to reduced water permeability caused by evapotranspiration-induced soil suction as well as foliage interception. However, the distributions of grass-induced suction in various compacted soils during rainfall are rarely reported. Moreover, it is not straightforward to determine an optimum soil dry density for minimizing rainfall infiltration and at the same time encouraging plant growth. This is because there are conflicting requirements for vegetated cover systems, i.e., compacted soil should not be too dense as to impede root growth, while on the other hand to minimize infiltration. This study thus aims to investigate, quantify, and compare grass-induced suction distributions in silty sand compacted at different densities when subjected to artificial rainfall in the laboratory. A grass species, Cynodon dactylon, which is common in many parts of Asia, was selected for testing. Compacted soil with and without a growing grass patch was tested at three relative compactions (RCs) of 70%, 80%, and 95%, in six test boxes. Test results reveal that at an RC of 95%, suction ( 40 kPa) retained in vegetated soil after rainfall is 100% higher than that ( 20 kPa) in bare soil. Among the vegetated soil compacted at the three RCs, suction retained was the highest at an RC of 95% ( 40 kPa), whereas suction decreased to 0 kPa at an RC of 70% after rainfall. As the average depth of grass roots decreased by 36% due to an increase in RC from 70% to 95%, the depth of influence of suction for vegetated soil at an RC of 95% reduced to less than half of root depth, which was the shallowest among the three compacted soil specimens

Effects of grass transpiration on suction induced in near-saturated soil condition

Plant transpiration is generally known to desiccate soil and increase matric suction through root-water uptake process. Research from the agricultural discipline has identified that the root-water uptake action may be suppressed in soil which is close to saturation condition due to limited oxygen diffusion. However, grass-induced suction recovery at low suction, which may be beneficial to slope stability, is not well understood and requires further investigation. This study aimed to measure grass-induced suction influence zone both vertically and laterally in the near-saturated soil condition. Rectangular test boxes were compacted with completely decomposed saprolite (silty sand) and seeds of bermudagrass were germinated within a ring collar. The vegetated specimen was irrigated with substantial amount of water to establish the near-saturated condition and then allowed to dry for a week naturally. Variation of matric suction was measured in vegetated specimens and was compared with the bare soil as control under the same controlled atmospheric condition

Experimental investigation of induced suction distributions in a grass-covered soil

Evapotranspiration from a grass-covered ground is known to induce suction by soil evaporation and grass transpiration. However, grass-induced suction in the ground when it is subjected to wetting and drying are not yet well understood. In this study, a laboratory test program was conducted to investigate the magnitude and distribution of suction induced by Bermuda grass growing in silty sand. In total, four test boxes compacted with silty sand were prepared, three of which covered with Bermuda grass while one test box was left bare as control. All the four test boxes were subjected to wetting and drying in a plant room with temperature and humidity controlled. Under identical atmospheric conditions and initial soil density and water content, peak suction induced within the root zone in grassed soil was 1.5 times higher than that in bare soil after 20 days of drying. A vertical suction influence zone was identified to be up to four times the root depth while the lateral suction influence zone was one diameter of ring collar away from the centre of the plot. Upon wetting, suction retained at depth right below the root zone in grassed soil was found to be 40% higher than that in bare soil. For three grass replicates that were germinated under identical atmospheric conditions, they produced different shoot lengths and induced different magnitudes of suction. No direct correlation between grass shoot length and grass-induced suction could be found. (c) 2012 Elsevier B.V. All rights reserved