A More Universal Approach to Comprehensive Analysis of Thalassemia Alleles (CATSA).

The aim of the study was to assess the clinical utility of a third-generation sequencing (TGS) approach termed comprehensive analysis of thalassemia alleles (CATSA) for identifying both α and ß thalassemia genetic carrier status. Prospective blood samples (n = 1759) with abnormal hemoglobin parameters were screened for pathogenic thalassemia variants by CATSA on the PacBio TGS platform. In 1159 individuals, a total of 1317 pathogenic thalassemia variants were identified and confirmed by independent PCR-based tests. Of the total thalassemia variants detected, the α-variant --SEA (35.4%) and ß-variant c.126_129delCTTT (15%) were the most common. CATSA was also able to detect three types of rare HBA structural variants as well as five rare HBA2, three HBA1, and 10 HBB single-nucleotide variations/insertions and deletions. Compared with standard thalassemia variant PCR panel testing, CATSA identified all panel variants present, with no false-negative results. Carrier assignment was improved through identification of rare variants missed by the panel test. On the basis of allelic coverage, reliability, and accuracy, TGS with long-range PCR presents a comprehensive approach with the potential to provide a universal solution for thalassemia genetic carrier screening. It is proposed that CATSA has immediate clinical utility as an effective carrier screening approach for at-risk couples.

Spatial Variability of Nitrate and Ammonium in Pleistocene Aquifer of Central Yangtze River Basin.

It becomes increasingly important and challenging for nitrogen pollution prevention to identify key controls for spatial variability of nitrogen in groundwater that could be affected by multiple factors, including anthropogenic input, groundwater flow, and local geochemistry. This study characterized spatial variability of both nitrate and ammonium in the Pleistocene aquifer of central Yangtze River Basin and assessed the effect of various factors in controlling nitrate and ammonium levels based on multiple statistical approaches (correlation, geostatistics, multiple liner regression). The results indicate that nitrate is mostly influenced by Cl- that represents anthropogenic input, while Eh representing local redox state is a secondary variable influencing nitrate concentrations. The groundwater with elevated nitrate concentrations are estimated to occur mainly in areas with higher-permeability near-surface sediments which can facilitate more anthropogenic nitrate transport and less nitrate removal owing to more oxidized state. Ammonium is mostly correlated to Eh, followed by dissolved organic carbon (DOC), but only DOC improves significantly the accuracy of co-kriging prediction model. The groundwater with elevated ammonium concentrations are estimated to occur mainly in areas with more organic-rich sediments within or around the aquifer which can facilitate more ammonium release owing to natural organic matter consumption accompanying strong reducing conditions. The regional groundwater flow is not a factor significantly controlling nitrate or ammonium levels owing to flat topography and sluggish lateral flow.

Hydrogeochemical evidences for targeting sources of safe groundwater supply in arsenic-affected multi-level aquifer systems.

Delineation of safe aquifers becomes highly imperative and challenging to ensure sustainable drinking water supply in rural areas of multi-level aquifer systems with complex water circulation under the impact of both geogenic and anthropogenic contamination. This work characterized hydrogeological and hydrogeochemical features of a multi-level Quaternary aquifer system of the central Yangtze River Basin to search for evidences of locating aquifers least contaminated. The results indicate modern hydrologic cycling is active in shallow phreatic aquifer (SPA) and in upper part of middle confined aquifer (MCA-1). The lower part of middle confined aquifer (MCA-2) and deep confined aquifer (DCA) have ages ranging from 200 to 2000 years and 4000 to >20,000 years, respectively. Vertical variations of hydrochemical compositions and Cl/Br ratios suggest the gradually decreasing and increasing contribution with depth from anthropogenic activities and natural water-mineral interactions, respectively. The SPA is characterized by high levels of anthropogenic components (Cl-, SO42-, NO3-, organic pesticides and antibiotics). The MCA-1 is the main aquifer where most private tube wells were installed, typically contains geogenic As, Fe, Mn and NH4+ at concentration levels several hundred times higher than the national drinking water standard values. Organic-abundant geochemical and stagnant hydrogeological conditions favor their enrichment. Both MCA-2 and DCA are slightly influenced by geogenic contamination and groundwater pumping from public wells screened in MCA-2 does not or slightly perturbs the groundwater flow condition in MCA-2 and DCA. The cost-effective water supply strategy is either to maintain safe yield of groundwater from public wells screened in MCA-2, or to use the groundwater after simple filtration and aeration treatment in case that groundwater pumping in MCA-2 were over a "safe yield" or induced leakage of groundwater containing As, Fe, Mn and NH4+ from the overlying MCA-1. And DCA could serve as a source for water supply under emergency circumstances.

Sources and fate of high levels of ammonium in surface water and shallow groundwater of the Jianghan Plain, Central China.

High levels of ammonium from anthropogenic sources threaten the quality of surface waters and groundwaters in some areas worldwide, but elevated ammonium levels of natural sources also have been identified. High levels of ammonium have been detected in both surface water and shallow groundwater of the Jianghan Plain, an alluvial plain of the Yangtze River. This study used N isotopes coupled with ancillary chemistry to identify ammonium in this region. Ammonium in the Tongshun River (up to 10.25 mg L-1) showed a sharp accumulation in the upstream and gradual attenuation in the downstream. The δ15N values of ammonium in the TSR were high and ranged narrowly from +12.5 to +15.4‰, suggesting an anthropogenic source that was septic effluent from industrial waste discharge. Sorption and nitrification were likely to respectively serve as the principal processes contributing to ammonium attenuation in different reaches of the downstream TSR. In shallow groundwater, high levels of ammonium (up to 14.10 mg L-1) occurred in a reducing environment. The narrow δ15N variation with low values (+2.3 to +4.5‰) in the lower aquifer suggested a natural source that was organic N mineralization. The δ15N values in the shallow aquitard exhibited a wide range from -1.8 to +9.4‰, owing to various sources. Two types of water in the shallow aquitard could be identified: (1) type-1 water with relatively longer residence time was similar to those in the aquifer where ammonium was mainly sourced from organic N mineralization; (2) type-2 water with shorter residence time was jointly affected by surface input, chemical attenuation and mineralization of organic N. The aquitard prevents prompt ammonium exchange between the surface and aquifer, and the shallower part of the aquitard provides a sufficient reaction time and an active reaction rate for ammonium removal.