Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.

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The variability and trend in global precipitable water vapor (PWV) from 1979 to 2014 are analyzed using the PWV data sets from the ERA‐Interim reanalysis of the European Centre for Medium‐Range Weather Forecasts (ECMWF), reanalysis of the National Centers for Environmental Prediction (NCEP), radiosonde, Global Positioning System (GPS), and microwave satellite observations. PWV data from the ECMWF and NCEP have been evaluated by radiosonde, GPS, and microwave satellite observations, showing that ECMWF has higher accuracy than NCEP. Over the oceans, ECMWF has a much better agreement with the microwave satellite than NCEP. An upward trend in the global PWV is evident in all the five PWV data sets over three study periods: 1979–2014, 1992–2014, and 2000–2014. Positive global PWV trends, defined as percentage normalized by annual average, of 0.61 ± 0.33% decade−1, 0.57 ± 0.28% decade−1, and 0.17 ± 0.35% decade−1, have been derived from the NCEP, radiosonde, and ECMWF, respectively, for the period 1979–2014. It is found that ECMWF overestimates the PWV over the ocean prior to 1992. Thus, two more periods, 1992–2014 and 2000–2014, are studied. Increasing PWV trends are observed from all the five data sets in the two periods: 1992–2014 and 2000–2014. The linear relationship between PWV and surface temperature is positive over most oceans and the polar region. Steep positive/negative regression slopes are generally found in regions where large regional moisture flux divergence/convergence occurs.

Tropospheric path delay is an important error source in range measurements of many Earth observation systems. In this paper, the accuracy of 9 zenith hydrostatic delay (ZHD) and 18 zenith wet delay (ZWD) models are assessed using benchmark values derived from 10 years (2003-2012) of radiosonde data recorded at 92 stations in China region. Our study confirms that ZHD can be well modeled with an accuracy of several millimeters by using surface meteorological observations. ZHD derived from the European Center for Medium-Range Weather Forecasts (ECMWF) has the best agreement of 2.8 mm with the radiosonde data in China region, while the Baby ZHD model achieves the second-best with an accuracy of 6.0 mm. All the ZWD models can only estimate the ZWD with an accuracy of a few centimeters. ECMWF can provide ZWD estimation with the best accuracy of 21.4 mm, followed by the Baby semi-empirical, Hopfield, Goad and Goodman, Askne and Nordius, Saastamoinen, Callahan, and Berman 74 ZWD models whose errors are below 40 mm. We find that in China region all the ZWD models perform better in winter than in summer and have higher accuracy in high latitudes than low latitudes. The performance of the 18 ZWD models are further validated in a Global Positioning System (GPS) precise point positioning (PPP) computation at 6 GPS stations in China. The PPP results also confirm that ECMWF is the best model. Considering its performance and simplicity, we conclude that Saastamoinen is the optimal ZWD model for the China region.

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