METHODS: Plasma samples were collected in a randomised, placebo-controlled, double-blind, cross-over trial (DIAMOND, NCT03190694, n = 53) that assessed the effects of 10 mg of dapagliflozin in patients with a glomerular filtration rate ≥ 25 mL/min/1.73 m2 and proteinuria > 500 mg/day. Mixed-effects models were used to develop a pharmacokinetic model and to evaluate the association between plasma exposure and response.
RESULTS: Plasma concentrations (n = 430 observations) from 48 patients (mean age 50.8 years, mean glomerular filtration rate 57.9 mL/min/1.73 m2, median proteinuria 1115 mg/24 h) were best described using a two-compartment model with first-order elimination. Apparent clearance and volume of distribution were 11.7 (95% confidence interval 10.7-12.7) L/h and 44.9 (95% confidence interval 39.0-50.9) L, respectively. Median dapagliflozin plasma exposure was 740.9 ng h/mL (2.5th-97.5th percentiles: 434.0-1615.3). Plasma exposure increased with decreasing kidney function. Every 100-ng h/mL increment in dapagliflozin plasma exposure was associated with a decrease in the urinary albumin:creatinine ratio (β = - 2.8%, p = 0.01), glomerular filtration rate (β = - 0.5 mL/min/1.73 m2, p
FINDINGS: We present a draft genome assembly that includes 200 Gb of Illumina reads, 4 Gb of Moleculo synthetic long reads, and 108 Gb of Chicago libraries, with a final size matching the estimated genome size of 2.7 Gb, and a scaffold N50 of 4.8 Mb. We also present an alternative assembly including 27 Gb raw reads generated using the Pacific Biosciences platform. In addition, we sequenced the proteome of the same individual and RNA from 3 different tissue types from 3 other species of squid (Onychoteuthis banksii, Dosidicus gigas, and Sthenoteuthis oualaniensis) to assist genome annotation. We annotated 33,406 protein-coding genes supported by evidence, and the genome completeness estimated by BUSCO reached 92%. Repetitive regions cover 49.17% of the genome.
CONCLUSIONS: This annotated draft genome of A. dux provides a critical resource to investigate the unique traits of this species, including its gigantism and key adaptations to deep-sea environments.
STUDY DESIGN: Data on ID were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 and estimated by age, sex, geographical region, and sociodemographic index (SDI).
METHODS: The estimated annual percentage change (EAPC) was calculated to evaluate the changing trend of age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), and age-standardized DALYs rate (ASDR) related to ID during the period 1990-2019.
RESULTS: In Asia, there were 126,983,965.8 cases with 5,466,213.1 new incidence and 1,765,995.5 DALYs of ID in 2019. Between 1999 and 2019, the EAPC in ASIR, ASPR and ASDR were -0.6 (95% confidence interval [CI], -0.8 to -0.4), -0.9 (95% CI, -1.2 to -0.7), and -1.6 (95% CI, -1.8 to -1.5), respectively. Malaysia charted the largest decrease in ASIR, ASPR, and ASDR (82.4%, 85.3%, and 80.9% separately), whereas the Philippines and Pakistan were the only two countries that witnessed an increase in ASIR and ASPR. ID burdens were more pronounced in women, countries located to the south of the Himalayas, and low-middle SDI regions.
CONCLUSIONS: The incidence, prevalence, and DALYs of ID in Asia substantially decreased from 1990 to 2019. Women and low-middle SDI countries have relatively high ID burdens. Governments need to pay constant attention to the implementation and monitoring of universal salt iodization.