Current status and challenges in prenatal and neonatal screening, diagnosis, and management of congenital heart disease in China.

Congenital heart disease (CHD), a wide spectrum of diseases with varied outcomes, is the most common congenital malformation worldwide. In this Series of three papers, we describe the burden of CHD in China; the development of screening, diagnosis, treatment, and follow-up strategies; and challenges associated with the disease. We also propose solutions and recommendations for policies and actions to improve the outcomes of CHD. In the first paper in this Series, we focus on prenatal and neonatal screening, diagnosis, and management of CHD. Based on advanced international knowledge, the Chinese Government has developed a network system comprising prenatal screening, diagnosis of CHD subtypes, specialist consultation appointments, and treatment centres for CHD. A new professional discipline, fetal cardiology, has been formed and rapidly developed. Consequently, the overall coverage of prenatal and neonatal screening and the accuracy of CHD diagnoses have gradually improved, and the neonatal CHD mortality rate has decreased substantially. However, China still faces several challenges in the prevention and treatment of CHD, such as insufficient diagnostic capabilities and unqualified consultation services in some regions and rural areas. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Algorithm for optimized mRNA design improves stability and immunogenicity.

Messenger RNA (mRNA) vaccines are being used to combat the spread of COVID-19 (refs. 1-3), but they still exhibit critical limitations caused by mRNA instability and degradation, which are major obstacles for the storage, distribution and efficacy of the vaccine products4. Increasing secondary structure lengthens mRNA half-life, which, together with optimal codons, improves protein expression5. Therefore, a principled mRNA design algorithm must optimize both structural stability and codon usage. However, owing to synonymous codons, the mRNA design space is prohibitively large-for example, there are around 2.4 × 10632 candidate mRNA sequences for the SARS-CoV-2 spike protein. This poses insurmountable computational challenges. Here we provide a simple and unexpected solution using the classical concept of lattice parsing in computational linguistics, where finding the optimal mRNA sequence is analogous to identifying the most likely sentence among similar-sounding alternatives6. Our algorithm LinearDesign finds an optimal mRNA design for the spike protein in just 11 minutes, and can concurrently optimize stability and codon usage. LinearDesign substantially improves mRNA half-life and protein expression, and profoundly increases antibody titre by up to 128 times in mice compared to the codon-optimization benchmark on mRNA vaccines for COVID-19 and varicella-zoster virus. This result reveals the great potential of principled mRNA design and enables the exploration of previously unreachable but highly stable and efficient designs. Our work is a timely tool for vaccines and other mRNA-based medicines encoding therapeutic proteins such as monoclonal antibodies and anti-cancer drugs7,8.

Linear-Time Algorithms for RNA Structure Prediction.

RNA secondary structure prediction is widely used to understand RNA function. Existing dynamic programming-based algorithms, both the classical minimum free energy (MFE) methods and partition function methods, suffer from a major limitation: their runtimes scale cubically with the RNA length, and this slowness limits their use in genome-wide applications. Inspired by incremental parsing for context-free grammars in computational linguistics, we designed linear-time heuristic algorithms, LinearFold and LinearPartition, to approximate the MFE structure, partition function and base pairing probabilities. These programs are orders of magnitude faster than Vienna RNAfold and CONTRAfold on long sequences. More interestingly, LinearFold and LinearPartition lead to more accurate predictions on the longest sequence families for which the structures are well established (16S and 23S Ribosomal RNAs), as well as improved accuracies for long-range base pairs (500 + nucleotides apart). This chapter provides protocols for using LinearFold and LinearPartition for secondary structure prediction.

Non-invasive prenatal testing for the detection of trisomy 13, 18, and 21 and sex chromosome aneuploidies in 68,763 cases.

Objectives: Non-invasive prenatal testing (NIPT) has been widely used in recent years. According to clinical experience from all hospitals providing prenatal screening services in Beijing, we explored the feasibility of using NIPT for the analysis of common foetal aneuploidies among pregnancies. Methods: In total, 68,763 maternal blood samples were collected from January 2020 to December 2020 at the Beijing prenatal diagnosis agency. Cases with positive screening results by NIPT detection were validated using prenatal diagnosis. Results: In total, 920 cases had a high-risk NIPT result, and 755 cases were shown to be truly positive by a chromosome karyotyping analysis; the prenatal diagnosis rate was 82.07% (755/920). Of the920 cases, there were 164 cases of T21, 70 cases of T18, 38 cases of T13, 360 cases of SCAs and 288 cases of other chromosomal abnormalities. The positive rates of T21, T18, T13, and SCAs were 0.24% (164/68,763), 0.10% (70/68,763), 0.06% (38/68,763) and 0.52% (360/68,763), respectively. The sensitivity and specificity were 98.17% and 99.92% for T21, 96.15% and 99.93% for T18, and 100% and 99.95% for T13, respectively. The PPVs of T21,T18,T13 and SCAs were65.24% (107/164), 35.71% (25/70), 18.42% (7/38) and 31.39% (113/360), respectively. For all indications, there were more higher T21/18/13 in the high-risk group than in the low-risk group (comprising only cases of voluntary request), with a positive rate of 0.46% vs. 0.27% (p < 0.001), sensitivity of 99.16% vs. 91.30% (p = 0.02) and PPV of 56.73%vs.32.81% (p = 0.001), but there was no significant difference in specificity between the groups (p = 0.71). The detection indication with the highest PPV (100%) by NIPT was ultrasound structural abnormalities and ultrasound soft marker abnormalities for T21 and ultrasound structural abnormalities and NT thickening for T18 and T13. The PPVs of different clinical indications of T21 (p = 0.002), T13 (p = 0.04) and SACs (p = 0.02) were statistically significant. Conclusion: The high specificity, efficiency and safety (non-invasiveness) of NIPT can effectively improve the detection rate of common chromosomal aneuploidy, thereby reducing the occurrence of birth defects. We should encourage pregnant women with NIPT-high-risk results to undergo a prenatal diagnosis to determine whether the foetus has chromosomal abnormalities. More importantly, the screening efficiency of NIPT in the low-risk group was significantly lower than that in the high-risk group. Therefore, the use of NIPT in low-risk groups should be fully promoted, and socioeconomic benefits should be considered.

LinearTurboFold: Linear-time global prediction of conserved structures for RNA homologs with applications to SARS-CoV-2.

The constant emergence of COVID-19 variants reduces the effectiveness of existing vaccines and test kits. Therefore, it is critical to identify conserved structures in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes as potential targets for variant-proof diagnostics and therapeutics. However, the algorithms to predict these conserved structures, which simultaneously fold and align multiple RNA homologs, scale at best cubically with sequence length and are thus infeasible for coronaviruses, which possess the longest genomes (∼30,000 nt) among RNA viruses. As a result, existing efforts on modeling SARS-CoV-2 structures resort to single-sequence folding as well as local folding methods with short window sizes, which inevitably neglect long-range interactions that are crucial in RNA functions. Here we present LinearTurboFold, an efficient algorithm for folding RNA homologs that scales linearly with sequence length, enabling unprecedented global structural analysis on SARS-CoV-2. Surprisingly, on a group of SARS-CoV-2 and SARS-related genomes, LinearTurboFold's purely in silico prediction not only is close to experimentally guided models for local structures, but also goes far beyond them by capturing the end-to-end pairs between 5' and 3' untranslated regions (UTRs) (∼29,800 nt apart) that match perfectly with a purely experimental work. Furthermore, LinearTurboFold identifies undiscovered conserved structures and conserved accessible regions as potential targets for designing efficient and mutation-insensitive small-molecule drugs, antisense oligonucleotides, small interfering RNAs (siRNAs), CRISPR-Cas13 guide RNAs, and RT-PCR primers. LinearTurboFold is a general technique that can also be applied to other RNA viruses and full-length genome studies and will be a useful tool in fighting the current and future pandemics.

LinearTurboFold: Linear-Time Global Prediction of Conserved Structures for RNA Homologs with Applications to SARS-CoV-2.

The constant emergence of COVID-19 variants reduces the effectiveness of existing vaccines and test kits. Therefore, it is critical to identify conserved structures in SARS-CoV-2 genomes as potential targets for variant-proof diagnostics and therapeutics. However, the algorithms to predict these conserved structures, which simultaneously fold and align multiple RNA homologs, scale at best cubically with sequence length, and are thus infeasible for coronaviruses, which possess the longest genomes (∼30,000 nt ) among RNA viruses. As a result, existing efforts on modeling SARS-CoV-2 structures resort to single sequence folding as well as local folding methods with short window sizes, which inevitably neglect long-range interactions that are crucial in RNA functions. Here we present LinearTurboFold, an efficient algorithm for folding RNA homologs that scales linearly with sequence length, enabling unprecedented global structural analysis on SARS-CoV-2. Surprisingly, on a group of SARS-CoV-2 and SARS-related genomes, LinearTurbo-Fold's purely in silico prediction not only is close to experimentally-guided models for local structures, but also goes far beyond them by capturing the end-to-end pairs between 5' and 3' UTRs (∼29,800 nt apart) that match perfectly with a purely experimental work. Furthermore, LinearTurboFold identifies novel conserved structures and conserved accessible regions as potential targets for designing efficient and mutation-insensitive small-molecule drugs, antisense oligonucleotides, siRNAs, CRISPR-Cas13 guide RNAs and RT-PCR primers. LinearTurboFold is a general technique that can also be applied to other RNA viruses and full-length genome studies, and will be a useful tool in fighting the current and future pandemics. SIGNIFICANCE STATEMENT: Conserved RNA structures are critical for designing diagnostic and therapeutic tools for many diseases including COVID-19. However, existing algorithms are much too slow to model the global structures of full-length RNA viral genomes. We present LinearTurboFold, a linear-time algorithm that is orders of magnitude faster, making it the first method to simultaneously fold and align whole genomes of SARS-CoV-2 variants, the longest known RNA virus (∼30 kilobases). Our work enables unprecedented global structural analysis and captures long-range interactions that are out of reach for existing algorithms but crucial for RNA functions. LinearTurboFold is a general technique for full-length genome studies and can help fight the current and future pandemics.

[Prediction of Prenatal Ultrasound Screening Staff's Situation in Beijing Based on ARIMA Model].

Objective To understand the current situation and predict the trends in number and composition of prenatal ultrasound screening staff in Beijing. Methods We analyzed the region,age,professional title and other characteristics of prenatal ultrasound screening personnel in Beijing during 2007-2015.We then built an ARIMA model basing on the current situation to predict the number and composition of the staff in 2016-2020. Results The number of prenatal ultrasound screening staff showed an upward trend in 2007-2020 and was predicted to reach 1269 in 2020.During this period,the educational achievement and professional title of the staff showed a downward trend,and the working years became shorter,mainly below 5 years.The proportion of resident doctors remained at 26.6%,and that of the staff receiving further education would reach 43.2% by the end of 2020. Conclusion The prediction under ARIMA model suggests that efforts should be made to strengthen the training of young doctors and provide them opportunities for further study.

Delayed diagnosis of critical congenital heart defects predicting risk factors and survival rate in newborns in Beijing: a retrospective study.

OBJECTIVE: To assess the prevalence and survival rate of newborns with a delayed diagnosis of critical congenital heart defects (CCHD) in Beijing. METHODS: This retrospective study analysed data from births between 2010 and 2017 from the Birth Defects Monitoring Network in Beijing. Newborns with CCHD were analysed according to seven categories. Statistical analyses were used to calculate the mortality rate within the first week (days 0-6) after live birth. Multivariate logistic regression analysis of survival was performed to analyse the potential risk factors for newborn mortality. RESULTS: A total of 1 773 935 perinatal newborns were screened in Beijing and 1851 newborns were diagnosed with CCHD, showing a prevalence of 10.43 per 10 000. Among the total 1851 CCHD patients, the majority (1692 of 1851; 91.41%) were identified through prenatal diagnosis, 104 of 1851 (5.62%) were diagnosed before obstetric discharge/transfer and 55 of 1851 (2.97%) were identified through delayed diagnosis. The prevalence of CCHD in newborns was 1.96 per 10 000 births. Multivariate logistic regression analysis of survival demonstrated that gestational age at delivery was the only risk factor for death within the first week after birth. CONCLUSIONS: Within the first week after birth, gestational age was the only risk factor for death in newborns with CCHD.

Birth defects surveillance after assisted reproductive technology in Beijing: a whole of population-based cohort study.

OBJECTIVES: To compare the differences in the prevalence of birth defects among offspring conceived by assisted reproductive technology (ART) and conceived spontaneously (non-ART), and assess the contribution of ART to birth defects. DESIGN: A population-based retrospective cohort study. SETTING: Beijing. PARTICIPANTS: Pregnant women whose expected date of childbirth was verified as occurring between October 2014 and September 2015, and were registered on the Beijing Maternal and Child Health Information Network System, were the recorded pregnancy outcomes. 2699 ART offspring and 191 368 non-ART offspring (live births, stillbirths and medical terminations) were included in our study. INTERVENTIONS: None. OUTCOME MEASURES: Risk ratios (RR) for birth defects were calculated among ART conceptions and non-ART conceptions with confounding factors by using logistic regression models. RESULTS: 194 067 offspring were included in the present study, and 2699 (1.4%) were conceived using ART. Among all the births, the prevalence of any birth defect in the ART offspring (5.5%) was significantly higher than in the non-ART offspring (3.8%) (crude RR, 1.49, 95% CI 1.26 to 1.76). After adjusting for confounding factors, ART use was still associated with an increased risk of any birth defect (5.4% vs 3.5% in ART and non-ART group, adjusted RR (aRR), 1.43, 95% CI 1.08 to 1.90), especially for chromosomal abnormalities (0.5% vs 0.2% in ART and non-ART group, aRR, 3.11, 95% CI 1.28 to 7.58), in singleton births to mothers <35 years. Circulatory system malformations and musculoskeletal system malformations were observed to have a non-significant increase in offspring conceived by ART. However, the associations between ART and birth defects were not detected in multiple births or mothers ≥35 years. CONCLUSIONS: This study confirmed a small but significant association between ART and birth defects. However, the risk tends to be non-significant under the conditions of advanced maternal age or multiple pregnancies.

Transfer learning of memory kernels for transferable coarse-graining of polymer dynamics.

The present work concerns the transferability of coarse-grained (CG) modeling in reproducing the dynamic properties of the reference atomistic systems across a range of parameters. In particular, we focus on implicit-solvent CG modeling of polymer solutions. The CG model is based on the generalized Langevin equation, where the memory kernel plays the critical role in determining the dynamics in all time scales. Thus, we propose methods for transfer learning of memory kernels. The key ingredient of our methods is Gaussian process regression. By integration with the model order reduction via proper orthogonal decomposition and the active learning technique, the transfer learning can be practically efficient and requires minimum training data. Through two example polymer solution systems, we demonstrate the accuracy and efficiency of the proposed transfer learning methods in the construction of transferable memory kernels. The transferability allows for out-of-sample predictions, even in the extrapolated domain of parameters. Built on the transferable memory kernels, the CG models can reproduce the dynamic properties of polymers in all time scales at different thermodynamic conditions (such as temperature and solvent viscosity) and for different systems with varying concentrations and lengths of polymers.

Epidemiological Aspects, Prenatal Screening and Diagnosis of Congenital Heart Defects in Beijing.

Background: In China, congenital heart disease (CHD) is the most common birth defect type, with approximately 13,000 new cases annually. This study aimed to investigate high-risk factors, prenatal screening and prenatal diagnosis as a basis for clinical decisions. Methods: All CHD cases identified from 2018 to 2020 were obtained from the Beijing city birth defect surveillance system and prenatal diagnosis institutions. The prenatal CHD diagnosis was confirmed by fetal echocardiography and amniotic fluid or cord blood genetic examination. Chi-square, odds ratio (OR), 95% confidence interval (CI), and univariate and multivariate logistic analyses were used to explore the high-risk factors, prenatal screening and prenatal diagnosis of CHD. Results: In total, 6,786/594,860 fetuses with CHD were diagnosed by prenatal echocardiography. The average incidence of CHD was 11.4 per 1,000 births, with an increase of 30.7 per 1,000 births from 2018 to 2020 (P < 0.05); the average incidence of complex CHD (CCHD) was 2.02 per 1,000 births, with no significant change from 2018 to 2020 (P > 0.05). Women age ≥35 years (OR 1.06, 95% CI 0.77-1.46) was at higher risk of having babies with CHD than women aged 21-34 years. Overall, CHD incidence increased with maternal age (OR1.03, 95% CI 1.02-1.03). Additionally, women who had a non-local household registration (OR 1.16, 95% CI 1.10-1.22) or had diabetes mellitus (DM) (OR 1.16, 95% CI 0.96-1.25) were at higher risk of CHD. As an independent factor, CCHD was related to maternal age, DM, fetal gender, and maternal education level (all P < 0.05). The prenatal ultrasound screening detection rate of CCHD was 97.59%, which was far higher than that of total CHD (51.67%) (P < 0.001). The prenatal ultrasound diagnosis rate of CCHD was higher than that of simple CHD (P < 0.001), but the coincidence rate in the ultrasound diagnosis of CCHD was lower than that of simple CHD (P < 0.001). Prenatal genetic testing revealed chromosomal abnormalities in 25.62% (279/1089) of CHD cases with indications for a prenatal diagnosis. Conclusions: Maternal age, household registration and DM were related to CHD occurrence. Prenatal ultrasound screening is a highly effective method for CCHD diagnosis, and CHD fetuses should be closely evaluated to exclude chromosomal abnormalities.

CoV-Seq, a New Tool for SARS-CoV-2 Genome Analysis and Visualization: Development and Usability Study.

BACKGROUND: COVID-19 became a global pandemic not long after its identification in late 2019. The genomes of SARS-CoV-2 are being rapidly sequenced and shared on public repositories. To keep up with these updates, scientists need to frequently refresh and reclean data sets, which is an ad hoc and labor-intensive process. Further, scientists with limited bioinformatics or programming knowledge may find it difficult to analyze SARS-CoV-2 genomes. OBJECTIVE: To address these challenges, we developed CoV-Seq, an integrated web server that enables simple and rapid analysis of SARS-CoV-2 genomes. METHODS: CoV-Seq is implemented in Python and JavaScript. The web server and source code URLs are provided in this article. RESULTS: Given a new sequence, CoV-Seq automatically predicts gene boundaries and identifies genetic variants, which are displayed in an interactive genome visualizer and are downloadable for further analysis. A command-line interface is available for high-throughput processing. In addition, we aggregated all publicly available SARS-CoV-2 sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID), National Center for Biotechnology Information (NCBI), European Nucleotide Archive (ENA), and China National GeneBank (CNGB), and extracted genetic variants from these sequences for download and downstream analysis. The CoV-Seq database is updated weekly. CONCLUSIONS: We have developed CoV-Seq, an integrated web service for fast and easy analysis of custom SARS-CoV-2 sequences. The web server provides an interactive module for the analysis of custom sequences and a weekly updated database of genetic variants of all publicly accessible SARS-CoV-2 sequences. We believe CoV-Seq will help improve our understanding of the genetic underpinnings of COVID-19.

[Efficiency of Prenatal Ultrasound Screening Service in Beijing: A Malmquist-Data Envelopment Analysis].

Objective To analyze the efficiency of prenatal ultrasound screening service in Beijing and thus optimize the secondary prevention system for birth defects in Beijing. Methods Data were collected from the prenatal screening work reports of Beijing from 2010-2016.Key variables were extracted after data quality control.Data envelopment analysis was performed to analyze the efficiency and changing trend of ultrasound-based screening service and to compare the service efficiency between urban and suburban areas in Beijing. Results From 2010 to 2016,the technical efficiency of ultrasound screening services showed an increasing trend,and the geometric mean of technical efficiency in suburban areas was higher than that in urban areas.From 2010 to 2016,the total factor productivity of ultrasound screening service increased by 12.3% annually,in which the technical change increased by 12.0% annually;the technical efficiency increased by 0.3%,the pure technical efficiency increased by 13.9% annually,and the scale efficiency decreased by 0.4%.Conclusions The technical efficiency of ultrasound screening service in Beijing increased from 2010 to 2016,and the total factor productivity improved.Technical change and pure technical efficiency change were the main reasons for the improvement.The resource allocation should be further optimized to improve the scale efficiency and enhance the training of prenatal ultrasound screening technicians.

LinearFold: linear-time approximate RNA folding by 5'-to-3' dynamic programming and beam search.

MOTIVATION: Predicting the secondary structure of an ribonucleic acid (RNA) sequence is useful in many applications. Existing algorithms [based on dynamic programming] suffer from a major limitation: their runtimes scale cubically with the RNA length, and this slowness limits their use in genome-wide applications. RESULTS: We present a novel alternative O(n3)-time dynamic programming algorithm for RNA folding that is amenable to heuristics that make it run in O(n) time and O(n) space, while producing a high-quality approximation to the optimal solution. Inspired by incremental parsing for context-free grammars in computational linguistics, our alternative dynamic programming algorithm scans the sequence in a left-to-right (5'-to-3') direction rather than in a bottom-up fashion, which allows us to employ the effective beam pruning heuristic. Our work, though inexact, is the first RNA folding algorithm to achieve linear runtime (and linear space) without imposing constraints on the output structure. Surprisingly, our approximate search results in even higher overall accuracy on a diverse database of sequences with known structures. More interestingly, it leads to significantly more accurate predictions on the longest sequence families in that database (16S and 23S Ribosomal RNAs), as well as improved accuracies for long-range base pairs (500+ nucleotides apart), both of which are well known to be challenging for the current models. AVAILABILITY AND IMPLEMENTATION: Our source code is available at https://github.com/LinearFold/LinearFold, and our webserver is at http://linearfold.org (sequence limit: 100 000nt). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Surveillance of Maternal Syphilis in China: Pregnancy Outcomes and Determinants of Congenital Syphilis.

BACKGROUND We sought to describe the epidemiological characteristics of pregnant women with syphilis in Beijing, China, and to investigate the determinants of adverse pregnancy outcomes, including congenital syphilis. MATERIAL AND METHODS We used data from laboratory-confirmed syphilis-infected women who delivered between 2013 and 2015 and were registered in China's Information Management System for Prevention of Mother-to-Child Transmission of Syphilis. Sociodemographic, clinical, and prevention predictors of adverse pregnancy outcomes (i.e., congenital syphilis, neonatal death, and neonatal asphyxia) were assessed using multivariable regression analyses. RESULTS Among 807 eligible pregnant women with syphilis in Beijing, the maternal syphilis ratios increased from 1.1 (in 2013) to 1.4 (in 2015) per 1000 live births, while adverse pregnancy outcomes decreased, including congenital syphilis (1.3% to 0.4%), neonatal deaths (1.3% to 0%), and neonatal asphyxia (0.9% to 0%). Both prevention and treatment interventions increased, including antenatal testing (93.5% to 93.9%), any treatment (76.6% to 85.2%), adequate treatment (51.1% to 65.1%), and treatment initiated in the first trimester (30.7% to 42.8%). In the logistic regression analysis, higher maternal rapid plasma reagin antibody titers (aOR=1.1 95%CI=1.0-1.1) and third-trimester syphilis diagnosis (aOR=1.7 95%CI=1.1-2.6) were independent risk factors for adverse pregnancy outcomes. Protective factors included being married (aOR=0.4; 95%CI=0.2-0.6) and adequate prenatal treatment (aOR=0.3; 95%CI=0.1-0.7). CONCLUSIONS Integrated strategies for maternal syphilis control were associated with improved outcomes but must be strengthened. Future efforts should include education and outreach for antenatal care for at-risk women, syphilis screening at first antenatal care visit, immediate initiation of treatment, and syphilis screening extended to women presenting with miscarriage or stillbirth.

Impact of the 2008 Beijing Olympics on the risk of pregnancy complications.

Taking advantage of the natural experiment of the 2008 Beijing Olympics (August 8 to September 24), when air pollution levels decreased by 13% to 60%, the authors assessed whether having ≥1 pregnancy month during the Olympics was associated with decreased risks of hypertensive disorders (HDs) and/or fetal-placental conditions (FPCs). Singleton births to mothers with ≥1 pregnancy month in 2008 or 2009 (N = 56,155) were included. Using generalized additive models, the authors estimated the risk of HDs and FPCs associated with (1) the 2008 Olympics compared with the same dates in 2009, and (2) increased mean ambient PM10 (particulate matter with an aerodynamic diameter <10 µm), NO2 (nitrogen dioxide), and SO2 (sulfur dioxide) concentrations during each trimester. However, no association between HDs or FPCs and having any trimester during the 2008 Olympic period was found. This may, in part, be due to a small number of pregnancy complications in this population.

An Obstructive Sleep Apnea Detection Approach Using a Discriminative Hidden Markov Model From ECG Signals.

Obstructive sleep apnea (OSA) syndrome is a common sleep disorder suffered by an increasing number of people worldwide. As an alternative to polysomnography (PSG) for OSA diagnosis, the automatic OSA detection methods used in the current practice mainly concentrate on feature extraction and classifier selection based on collected physiological signals. However, one common limitation in these methods is that the temporal dependence of signals are usually ignored, which may result in critical information loss for OSA diagnosis. In this study, we propose a novel OSA detection approach based on ECG signals by considering temporal dependence within segmented signals. A discriminative hidden Markov model (HMM) and corresponding parameter estimation algorithms are provided. In addition, subject-specific transition probabilities within the model are employed to characterize the subject-to-subject differences of potential OSA patients. To validate our approach, 70 recordings obtained from the Physionet Apnea-ECG database were used. Accuracies of 97.1% for per-recording classification and 86.2% for per-segment OSA detection with satisfactory sensitivity and specificity were achieved. Compared with other existing methods that simply ignore the temporal dependence of signals, the proposed HMM-based detection approach delivers more satisfactory detection performance and could be extended to other disease diagnosis applications.

Differences in Birth Weight Associated with the 2008 Beijing Olympics Air Pollution Reduction: Results from a Natural Experiment.

BACKGROUND: Previous studies have reported decreased birth weight associated with increased air pollutant concentrations during pregnancy. However, it is not clear when during pregnancy increases in air pollution are associated with the largest differences in birth weight. OBJECTIVES: Using the natural experiment of air pollution declines during the 2008 Beijing Olympics, we evaluated whether having specific months of pregnancy (i.e., 1st…8th) during the 2008 Olympics period was associated with larger birth weights, compared with pregnancies during the same dates in 2007 or 2009. METHODS: Using n = 83,672 term births to mothers residing in four urban districts of Beijing, we estimated the difference in birth weight associated with having individual months of pregnancy during the 2008 Olympics (8 August-24 September 2008) compared with the same dates in 2007 and 2009. We also estimated the difference in birth weight associated with interquartile range (IQR) increases in mean ambient particulate matter ≤ 2.5 µm in aerodynamic diameter (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) concentrations during each pregnancy month. RESULTS: Babies whose 8th month of gestation occurred during the 2008 Olympics were, on average, 23 g larger (95% CI: 5 g, 40 g) than babies whose 8th month occurred during the same calendar dates in 2007 or 2009. IQR increases in PM2.5 (19.8 µg/m3), CO (0.3 ppm), SO2 (1.8 ppb), and NO2 (13.6 ppb) concentrations during the 8th month of pregnancy were associated with 18 g (95% CI: -32 g, -3 g), 17 g (95% CI: -28 g, -6 g), 23 g (95% CI: -36 g, -10 g), and 34 g (95% CI: -70 g, 3 g) decreases in birth weight, respectively. We did not see significant associations for months 1-7. CONCLUSIONS: Short-term decreases in air pollution late in pregnancy in Beijing during the 2008 Summer Olympics, a normally heavily polluted city, were associated with higher birth weight. CITATION: Rich DQ, Liu K, Zhang J, Thurston SW, Stevens TP, Pan Y, Kane C, Weinberger B, Ohman-Strickland P, Woodruff TJ, Duan X, Assibey-Mensah V, Zhang J. 2015. Differences in birth weight associated with the 2008 Beijing Olympics air pollution reduction: results from a natural experiment. Environ Health Perspect 123:880-887; http://dx.doi.org/10.1289/ehp.1408795.

Physician performance assessment using a composite quality index.

Assessing physician performance is important for the purposes of measuring and improving quality of service and reducing healthcare delivery costs. In recent years, physician performance scorecards have been used to provide feedback on individual measures; however, one key challenge is how to develop a composite quality index that combines multiple measures for overall physician performance evaluation. A controversy arises over establishing appropriate weights to combine indicators in multiple dimensions, and cannot be easily resolved. In this study, we proposed a generic unsupervised learning approach to develop a single composite index for physician performance assessment by using non-negative principal component analysis. We developed a new algorithm named iterative quadratic programming to solve the numerical issue in the non-negative principal component analysis approach. We conducted real case studies to demonstrate the performance of the proposed method. We provided interpretations from both statistical and clinical perspectives to evaluate the developed composite ranking score in practice. In addition, we implemented the root cause assessment techniques to explain physician performance for improvement purposes.