Noninvasive prenatal testing for the detection of fetal chromosome 17 microduplication: clinical implications and findings.

BACKGROUND:  Noninvasive prenatal testing (NIPT) is widely used to screen for fetal aneuploidies. However, there are few reports of using NIPT for screening chromosomal microduplications and microdeletions. This study aimed to investigate the application efficiency of NIPT for detecting chromosomal microduplications. METHODS: Four cases of copy number gains on the long arm of chromosome 17 (17q12) were detected using NIPT and further confirmed using copy number variation (CNV) analysis based on chromosome microarray analysis (CMA). RESULTS: The prenatal diagnosis CMA results of the three cases showed that the microduplications in 17q12 (ranging from 1.5 to 1.9 Mb) were consistent with the NIPT results. The karyotypic analysis excluded other possible unbalanced rearrangements. The positive predictive value of NIPT for detecting chromosomal 17q12 microduplication was 75.0%. CONCLUSIONS:  NIPT has a good screening effect on 17q12 syndrome through prenatal diagnosis, therefore it could be considered for screening fetal CNV during the second trimester. With the clinical application of NIPT, invasive prenatal diagnoses could be effectively reduced while also improving the detection rate of fetal CNV.

Individualized Implementation of Youth Quality of Life Instrument-Research Version (YQOL-R) Among Chinese Adolescents with Different Weight Status.

Purpose: This study implemented the individualized Youth Quality of Life Instrument-Research Version (YQOL-R) to estimate the quality of life (QoL) among Chinese adolescents with three different Body Mass Index (BMI) levels. The study aims to explore and provide a reference for developing individualized QoL (IQoL) measurements in China. Methods: The sample consisted of 822 aged 11-18 from nine schools. The data collection included all participants' primary characters (age, sex, annual household income, parental education, and recruitment community) and their self-report QoL. Precisely, based on the generic measurement of YQOL-R, we developed IQoL measurements by asking adolescents' perceived five most important things to them (IQOLimportance) and the aspects they most want to change (IQOLchange) from 19 facets, respectively. The one-way analysis of variance (ANOVA) was applied to compare total and subscale scores of IQOLimportance, IQOLchange, and YQOL-R among adolescents with three different weight status. Also, the data analysis used multivariable linear regression modeling to test the effects on scores of IQOLimportance and IQOLchange. Results: Overall, the obese adolescents identified "Having good physical health" as the most important (54.03%) and most like-to-change (42.65%); in contrast, the normal-weight group ranked "Being myself" as the top facet of IQOLimportance (52.42%) and "Having good friends" as the top facet of IQOLchange (43.12%). The obese adolescents' reported IQOLimportance scores are significantly lower than those of the normal-weight group (P=0.039). However, there is no significant difference in IQOLchange score among the three weight-status groups. The multivariable linear regression models indicated that adolescents who are girls (P=0.035), have higher educated fathers (P=0.049), and are overweight/obese (P=0.041) self-reported worse IQOLimportance score; yet, the girls (P=0.023) and older adolescents (P=0.004) answered lower IQOLchange scores. In addition, adolescents who had higher educated mothers (P=0.047; 0.023) and responded with higher total YQOL-R scores (P<0.001; <0.001) reported higher IQOLimportance and IQOLchange scores. Conclusion: In the current study, although the self-reported YQOL-R scores from different weight status did not present a significant difference, the obese group reported a statistical trend towards lower IQOLimportance scores than the normal-weight and overweight adolescents. These findings emphasize that IQOLimportance and IQOLchange could capture adolescents' perspectives with different weight statuses about their lives, which are unique as complementary health outcomes accompanying YQOL-R in health surveys and interventions among Chinese adolescents.

Clinical evaluation of NIPS for women at advanced maternal age: a multicenter retrospective study.

Objective: To explore the clinical effect of noninvasive prenatal screening (NIPS) for the women at advanced maternal age (AMA) and discuss the relationship between women's age and NIPS effect.Methods: Fourteen thousand thirty-five women at AMA who accepted NIPS from two prenatal diagnosis centers were recruited for this study. NIPS were checked by Illumina Next CN 500. All the AMA women received prenatal genetic counseling, selected prenatal diagnosis and different clinical treatments according to the results of NIPS.Results: A total of 114 cases (0.81%) got the NIPS-positive results of T21/T18/T13. One hundred four cases of them accepted prenatal diagnosis and 87 cases were proved as true positive. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 100, 99.88, 92.55 and 100%, respectively. Seventy-four women (0.53%) showed NIPS-positive results of sex chromosomal aneuploidies (SCAs). After informed consent, 46 women (62.2%) accepted fetus karyotype analysis. Nineteen cases were identified as true positive results, while 27 cases were false positive results. The PPV for SCAs in AMA women was 41.3%. The PPV of T21/T18/T13 in AMA women over 40 was 100%, while it was 81.91% for the women whose age was 35 ∼ 40 years old. There was also rising trend in PPV of fetal sex chromosome with the increased age (62.50 versus 36.84%).Conclusions: NIPS is a good choice for AMA pregnant women. It can not only achieve satisfactory clinical effect, but also greatly reduce invasive prenatal diagnosis. We will get better effect of NIPS by further managing AMA women stratified by their age.

Not all chromosome aberrations can be detected by NIPT in women at advanced maternal age: A multicenter retrospective study.

OBJECTIVE: To discuss the detectability of NIPT for pregnant women at advanced maternal age (AMA), and mainly focused on how many fetal abnormalities will be missed by NIPT. METHODS: A total of 4194 women at AMA who accepted cytogenetic prenatal diagnosis were recruited in this study. All the AMA women received amniocentesis at 18-23 weeks. Combined with our detection level of NIPT and literature reports, we evaluated the detectability of NIPT. RESULTS: After cell karyotype analysis, a total of 233 (5.56%) fetuses were confirmed to have chromosomal abnormalities, including 91.0% were abnormal chromosome number and 9.0% were abnormal chromosome structure. According to the detectability of NIPT we calculated, 87.6% abnormal results could also be detected by NIPT. However, NIPT would miss 12.4% abnormal results which could be originally found by the karyotype analysis of amniotic fluid cells. The major types of missed fetal abnormalities include structural rearrangement, mosaic and triploidy. Meanwhile, there were no relationship between the detectability of NIPT and the age of AMA pregnant women. CONCLUSIONS: About 12.4% of fetal chromosomal abnormalities will be missed if NIPT completely replaces invasive prenatal diagnosis in AMA women. Fortunately, these types of fetal abnormalities missed by NIPT did not increase with the age elevating of pregnant women.

Overall evaluation of the clinical value of prenatal screening for fetal-free DNA in maternal blood.

OBJECTIVE: To explore the clinical value of prenatal screening for fetal-free DNA in maternal blood. METHODS: A total of 10,275 maternal blood samples were collected from October 2012 to May 2016 at the prenatal diagnosis center of Changzhou Woman and Children Health Hospital. RESULTS: Among 10,275 pregnant women accepted noninvasive prenatal testing (NIPT), 9 cases could not get the results after collected the blood second times. The rate of NIPT failure was 0.09%. Seventy-two cases got the NIPT positive results of trisomy 21/trisomy 18/trisomy 13, and the detection rate, specificity, positive predictive value (PPV), and false positive rate were 98.59%, 99.99%, 97.22%, and 0.02%. The top-3 indications of the study were advanced age women (34.90%), high risk (25.22%), and intermediate risk (19.56%). They all had the satisfactory results of NIPT. Fifty-seven pregnant women had the high risk of fetal sex chromosomal aneuploidies (SCA). After informed consent, 33 cases accepted prenatal diagnosis. Eighteen cases were confirmed as sex chromosome aneuploidies. The PPV was 54.54%. Compared with other SCA, the PPV of Turner syndrome was lower. One case was false negative after followed up. CONCLUSIONS: NIPT showed a broad application prospects for prenatal screening and diagnosis of fetal chromosomal diseases. We should deepen mining and analyzing the clinical data, and explore the use of NIPT more reasonably from the perspective of evidence-based medicine.

Noninvasive prenatal screening for fetal common sex chromosome aneuploidies from maternal blood.

Objective To explore the feasibility of high-throughput massively parallel genomic DNA sequencing technology for the noninvasive prenatal detection of fetal sex chromosome aneuploidies (SCAs). Methods The study enrolled pregnant women who were prepared to undergo noninvasive prenatal testing (NIPT) in the second trimester. Cell-free fetal DNA (cffDNA) was extracted from the mother's peripheral venous blood and a high-throughput sequencing procedure was undertaken. Patients identified as having pregnancies associated with SCAs were offered prenatal fetal chromosomal karyotyping. Results The study enrolled 10 275 pregnant women who were prepared to undergo NIPT. Of these, 57 pregnant women (0.55%) showed fetal SCA, including 27 with Turner syndrome (45,X), eight with Triple X syndrome (47,XXX), 12 with Klinefelter syndrome (47,XXY) and three with 47,XYY. Thirty-three pregnant women agreed to undergo fetal karyotyping and 18 had results consistent with NIPT, while 15 patients received a normal karyotype result. The overall positive predictive value of NIPT for detecting SCAs was 54.54% (18/33) and for detecting Turner syndrome (45,X) was 29.41% (5/17). Conclusion NIPT can be used to identify fetal SCAs by analysing cffDNA using massively parallel genomic sequencing, although the accuracy needs to be improved particularly for Turner syndrome (45,X).

Factors influencing quality of life of obese students in Hangzhou, China.

OBJECTIVE: To evaluate the quality of life (QOL) of overweight and obese middle or high school students and identify relevant factors influencing their QOL scores. METHODS: 716 students were recruited from 6 middle or high schools in Hangzhou, China. The Chinese version of the Youth Quality of Life Instrument-Weight Module (YQOL-W) was self administered. The YQOL-W scores were compared among different BMI groups, gender, educational status, annual household income, parental education and recruitment community using t test or one-way analysis of variance. The independent association of these variables with QOL among overweight and obese students was examined using multivariable linear regression modeling. RESULTS: Overweight and obese students reported lower total scores, self, social and environment scores than their normal weight peers (all P<0.001). The QOL of overweight and obese middle and high school students was associated with BMI value, gender, educational status, parental education, and recruitment community. Girls had lower total scores, self, social and environment domain scores than boys (all P<0.001); high school students had lower total and three domain scores than middle school students (all P<0.05). Students whose fathers had higher education reported higher total scores, self and social scores than students with less educated fathers (all P<0.05). Students whose mothers had higher education reported higher environment scores than students with less educated mothers (P = 0.01). Students from migrant communities reported significantly lower total scores, self and social scores than those from rural communities (all P<0.05), but comparable scores with those from urban communities (P>0.05). Students from migrant communities reported comparable environment scores with those from rural and urban communities (P>0.05). CONCLUSIONS: Overweight and obesity have negative effects on students' quality of life. Therefore weight specific QOL could be included in weight reduction interventions as a relevant outcome.

Measurement properties of the Chinese version of the Youth Quality of Life Instrument-Weight Module (YQOL-W).

BACKGROUND: Childhood obesity is a growing public health concern in China. It not only compromises physical health, but also has negative impacts on psychosocial well-being. As obesity rates increase, finding out what the perceptions of Chinese youth are regarding their weight is important for intervention planning and evaluation. However, there is a paucity of available obesity-specific instruments for children and adolescents in China and youth weight-specific quality of life (QOL) has been little reported. This study aimed to evaluate the measurement properties of the Chinese version of the Youth Quality of Life Instrument - Weight Module (YQOL-W). METHODS: The Chinese version of the YQOL-W was administered to 840 youth aged 11-18 from nine schools. Measurement properties including measurement model, reliability, validity and burden were evaluated. RESULTS: Confirmatory factor analysis showed that a three-factor model had acceptable model fit. The instrument had robust internal consistency reliability with Cronbach's α ranging from 0.84 to 0.96 and acceptable test-retest reliability with the intraclass correlation coefficients (ICCs) all higher than 0.7. The standard error of measurement (SEM) values for the Self, Social and Environment factors and total score were 10.352, 9.526, 12.086 and 8.425, respectively. The small real differences (SRDs) for the Self, Social and Environment factors and total score were 28.675, 26.387, 33.478, and 23.337, respectively. The Pearson's correlation coefficients between the YQOL-W and the PedsQL4.0 General Core Scales were stronger between comparable dimensions than those between less comparable dimensions, demonstrating convergent and discriminant evidence of construct validity. Significant differences were found in subscale and total scores across weight status, age and genders (P<0.01), supporting the known-groups validity of the instrument. CONCLUSION: The Chinese version of the YQOL-W has acceptable measurement properties and can be used to assess the weight-specific QOL of children and adolescents in China.

[Current status of schistosomiasis control knowledge and effect of interventions among primary school pupils in Anyi County].

OBJECTIVE: To understand the status of schistosomiasis control knowledge and the effect of interventions among primary school pupils in the areas of schistosomiasis transmission interrupted. METHODS: Six kinds of information materials about schistosomiasis control, including the schistosomiasis health education teaching material, schistosomiasis health education box, schistosomiasis health education stationary kits, schistosomiasis health education ball-point pen, collections of wall charts about schistosomiasis control and schistosomiasis health education curriculum schedule, were used to spread the schistosomiasis control information in the experimental group, and then, the effect was evaluated. RESULTS: The awareness rates, correct rates of attitude, and persuasion rates of schistosomiasis control had no significant difference between the experimental group and control group before the intervention (P > 0.05). The awareness rate, correct rate of attitude, and persuasion rate of schistosomiasis control increased from 12.88%, 6.82% and 3.79% before the intervention to 97.64%, 62.20%, 71.65% after the intervention, respectively, in the experiment group (P < 0.01), but in the control group, there was no significant difference between the pre- and post-intervention (P > 0.05). The collections of wall charts about schistosomiasis control and schistosomiasis health education box were more favorable. CONCLUSION: The effect of schistosomiasis health education is very well in the areas of schistosomiasis transmission interrupted

Sensibility of linkage information and effectiveness of estimated distributions.

The probabilistic model building performed by estimation of distribution algorithms (EDAs) enables these methods to use advanced techniques of statistics and machine learning for automatic discovery of problem structures. However, in some situations, it may not be possible to completely and accurately identify the whole problem structure by probabilistic modeling due to certain inherent properties of the given problem. In this work, we illustrate one possible cause of such situations with problems consisting of structures with unequal fitness contributions. Based on the illustrative example, we introduce a notion that the estimated probabilistic models should be inspected to reveal the effective search directions and further propose a general approach which utilizes a reserved set of solutions to examine the built model for likely inaccurate fragments. Furthermore, the proposed approach is implemented on the extended compact genetic algorithm (ECGA) and experiments are performed on several sets of additively separable problems with different scaling setups. The results indicate that the proposed method can significantly assist ECGA to handle problems comprising structures of disparate fitness contributions and therefore may potentially help EDAs in general to overcome those situations in which the entire problem structure cannot be recognized properly due to the temporal delay of emergence of some promising partial solutions.

Enabling the extended compact genetic algorithm for real-parameter optimization by using adaptive discretization.

An adaptive discretization method, called split-on-demand (SoD), enables estimation of distribution algorithms (EDAs) for discrete variables to solve continuous optimization problems. SoD randomly splits a continuous interval if the number of search points within the interval exceeds a threshold, which is decreased at every iteration. After the split operation, the nonempty intervals are assigned integer codes, and the search points are discretized accordingly. As an example of using SoD with EDAs, the integration of SoD and the extended compact genetic algorithm (ECGA) is presented and numerically examined. In this integration, we adopt a local search mechanism as an optional component of our back end optimization engine. As a result, the proposed framework can be considered as a memetic algorithm, and SoD can potentially be applied to other memetic algorithms. The numerical experiments consist of two parts: (1) a set of benchmark functions on which ECGA with SoD and ECGA with two well-known discretization methods: the fixed-height histogram (FHH) and the fixed-width histogram (FWH) are compared; (2) a real-world application, the economic dispatch problem, on which ECGA with SoD is compared to other methods. The experimental results indicate that SoD is a better discretization method to work with ECGA. Moreover, ECGA with SoD works quite well on the economic dispatch problem and delivers solutions better than the best known results obtained by other methods in existence.

Particle swarm optimization with recombination and dynamic linkage discovery.

In this paper, we try to improve the performance of the particle swarm optimizer by incorporating the linkage concept, which is an essential mechanism in genetic algorithms, and design a new linkage identification technique called dynamic linkage discovery to address the linkage problem in real-parameter optimization problems. Dynamic linkage discovery is a costless and effective linkage recognition technique that adapts the linkage configuration by employing only the selection operator without extra judging criteria irrelevant to the objective function. Moreover, a recombination operator that utilizes the discovered linkage configuration to promote the cooperation of particle swarm optimizer and dynamic linkage discovery is accordingly developed. By integrating the particle swarm optimizer, dynamic linkage discovery, and recombination operator, we propose a new hybridization of optimization methodologies called particle swarm optimization with recombination and dynamic linkage discovery (PSO-RDL). In order to study the capability of PSO-RDL, numerical experiments were conducted on a set of benchmark functions as well as on an important real-world application. The benchmark functions used in this paper were proposed in the 2005 Institute of Electrical and Electronics Engineers Congress on Evolutionary Computation. The experimental results on the benchmark functions indicate that PSO-RDL can provide a level of performance comparable to that given by other advanced optimization techniques. In addition to the benchmark, PSO-RDL was also used to solve the economic dispatch (ED) problem for power systems, which is a real-world problem and highly constrained. The results indicate that PSO-RDL can successfully solve the ED problem for the three-unit power system and obtain the currently known best solution for the 40-unit system.

Convergence time for the linkage learning genetic algorithm.

This paper identifies the sequential behavior of the linkage learning genetic algorithm, introduces the tightness time model for a single building block, and develops the connection between the sequential behavior and the tightness time model. By integrating the first-building-block model based on the sequential behavior, the tightness time model, and the connection between these two models, a convergence time model is constructed and empirically verified. The proposed convergence time model explains the exponentially growing time required by the linkage learning genetic algorithm when solving uniformly scaled problems.