基于Mann-Kendall的广东省长效避孕服务利用和人工流产的趋势与突变分析

目的了解广东省长效避孕服务利用和人工流产变化趋势,为制定有效的生殖保健服务策略,提高妇女生殖健康提供依据。方法采用Mann-Kendall检验法对2008—2021年广东省长效避孕服务利用总例数、各种长效避孕方法例数与占比、人工流产例数、人工流产活产比进行趋势和突变分析。结果2008—2021年广东省长效避孕服务利用总例数呈现下降趋势,长效不可逆避孕方法例数呈先增后降的趋势、长效可逆避孕方法例数呈现下降趋势;这三个指标突变点分别出现在2016、2018、2014年。各种长效避孕方法服务利用上,放置宫内节育器术占67.3%,输卵管绝育术占29.1%,输精管绝育术占3.5%,放置皮下填埋剂术占0.1%。全省人工流产例数呈下降趋势,突变点出现在2018年;人工流产活产比相对稳定,年均人工流产活产比为76.5%。从区域层面看,全省与珠三角地区长效可逆避孕方法例数和人工流产例数的变化趋势呈现出平行关系,粤东、粤西和粤北地区长效可逆避孕方法例数变化趋势与人工流产例数变化趋势的关联各异。结论广东省放置宫内节育器术在长效避孕方法中占主导地位,输卵管绝育术次之,长效避孕责任主要由女性群体承担。区域间长效可逆避孕方法与人工流产变化趋势呈现出不同的关系,有必要深入了解导致这些地区差异的因素,促进不同区域避孕服务的有效落实,避免发生意外妊娠。此外,建议地区积极探讨将避孕服务与妇女全生命周期服务整合,提高妇女生殖健康水平。

Novel technique for cost reduction in mutation testing

Aimed at the problem of expensive costs in mutation testing which has hampered its wide use,a technique of introducing a test case selection into the process of mutation testing is proposed.For each mutant,a fixed number of test cases are selected to constrain the maximum allowable executions so as to reduce useless work.Test case selection largely depends on the degree of mutation.The mutation distance is an index describing the semantic difference between the original program and the mutated program.It represents the percentage of effective test cases in a test set,so it can be used to guide the selection of test cases.The bigger the mutation distance is,the easier it is that the mutant will be killed,so the corresponding number of effective test cases for this mutant is greater.Experimental results suggest that the technique can remarkably reduce execution costs without a significant loss of test effectiveness.

Genetic mutation of Tas2r104/Tas2r105/Tas2r114 cluster leads to a loss of taste perception to denatonium benzoate and cucurbitacin B

Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo.Methods:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes.Then,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice.Quantitative real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds.Perception to taste substance was also studied using twobottle preference tests.Results:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique.Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice.But qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant mice.With two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105.In addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception.Conclusions:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.

Study on MCM Interconnect Test Generation Based on Ant Algorithm with Mutation Operator

A novel multi-chip module(MCM) interconnect test generation scheme based on ant algorithm(AA) with mutation operator was presented.By combing the characteristics of MCM interconnect test generation,the pheromone updating rule and state transition rule of AA is designed.Using mutation operator,this scheme overcomes ordinary AA’s defects of slow convergence speed,easy to get stagnate,and low ability of full search.The international standard MCM benchmark circuit provided by the MCNC group was used to verify the approach.The results of simulation experiments,which compare to the results of standard ant algorithm,genetic algorithm(GA) and other deterministic interconnecting algorithms,show that the proposed scheme can achieve high fault coverage,compact test set and short CPU time,that it is a newer optimized method deserving research.

Towards Semantic Mutation Testing of Aspect-Oriented Programs

Aspect-oriented programs have received much attention from software testing researchers. Various testing techniques and approaches have been proposed to tackle issues and challenges when testing aspect-oriented programs including traditional mutation testing. In traditional mutation testing of aspect-oriented programs, mutants are generated by making small changes to the syntax of the aspect-oriented language. Recently, a new approach known as semantic mutation testing has been proposed. This approach mutates the semantics of the language in which the program is written. The mutants generated misunderstandings of the language which are different classes of faults. Aspect-oriented programming presents itself with different properties that can be further explored with respect to semantic mutation testing. This paper describes various possible scenarios that semantic mutation testing strategy might have particular value in testing aspect-oriented programs.

基于Mann-Kendall检验的香港鲗鱼涌地区降水与潮位变化趋势分析

香港鲗鱼涌地区是受气候与潮位变化影响较大的敏感区域。为研究降水量与潮位变化对该区域的影响情况,收集2006—2023年鲗鱼涌潮汐站观测的降水量与潮位数据,运用Mann-Kendall检验法分析降水量和潮位的年际、年内变化规律及突变特征。研究结果表明:2006—2023年,鲗鱼涌地区多年平均降水量2274.11 mm,平均潮位1.46 m,年内降水量分配不均匀,而年内平均潮位较均匀。年际尺度上,降水量变化较大,平均潮位变化较小,总体呈上升趋势;季际尺度和月际尺度上,潮位和降水量的变化趋势各异;年际潮位在2007—2008年出现突变特征,而年际降水量未出现突变特征。研究结果可为香港鲗鱼涌地区水资源管理和气候变化的应对决策提供科学依据。

Investigation into Recent Temperature and Rainfall Trends in Mali Using Mann-Kendall Trend Test: Case Study of Bamako

Rainfall and temperature variability analysis is important for researchers and policy formulators in making critical decisions on water availability and use in communities. The Western Sahel, which comprises Mali is considered as one of the vulnerable regions to climate change, and also encountered the challenges of climatic shocks such as flood and drought. This research therefore sought to investigate climate change effects on hydrological events and trends in Sahelian rainfall intensity using Bamako (Mali) as a case study from 1991 to 2020, as limited data availability did not allow an extended period of study. Monthly observed data provided by MALI-METEO was used to validate daily rainfalls data from African Rainfall Climatology Version 2 (ARC2) satellite-based rainfall product on monthly basis. The validated model performance used Nash-Sutcliffe Efficiency (NSE) and Percent Bias (PBAIS) and gave results of 0.904 and 1.0506 respectively. Trends in annual maximum temperatures and rainfalls were analyzed using Mann-Kendall trend test. The result indicated that the trend in annual maximum rainfalls was decreasing, while annual total rainfall was increasing but not significant at 5% significance level. The rate of increase in annual total rainfalls was 0.475 mm/year according to the observed annual rainfall series and decreased to 0.68 mm/year in annual maximum. The analysis further found that annual maximum temperatures were increasing at the rate of 0.03°C/year at 5% significance level. To provide more accurate climate predictions, it is recommended that further studies on rainfall and temperature with data sets spanning 60 - 90 years be carried out.

Temperature Variation and Mutation Analysis over the Past 59 Years in Shenyang

In this paper,based on the observation data of air temperature during 1951-2009 in Shenyang,the interannual and interdecadal variation of annual average temperature,maximum and minimum temperature in Shenyang were conducted the statistical analysis by means of linear trend estimation and mutation detection by using Mann-Kendall method.As was demonstrated in the results,the annual average temperature,maximum and minimum temperature in Shenyang showed an upward trend,whose linear tendency rate was 0.231,0.181 and 0.218 respectively.The increment trend of annual average temperature,maximum and minimum temperature was extremely clear.The increase in minimum temperature was more significant than that in mean temperature and maximum temperature.The abrupt change point of annual mean temperature in Shenyang appeared in 1981;the abrupt change point of annual mean maximum temperature appeared in 1994;the annual mean minimum temperature underwent mutation in 1978.

基于Daniel及Mann-kendall检验的辽西北地区降雨量趋势分析

为探索辽西北地区降雨特征及其发生规律,采用辽西北地区5个市21个气象站1952~2006年间的气象资料,应用Daniel及Mann-Kendall检验方法对辽西北地区降雨量的年际变化及季节变化趋势进行分析,并应用Mann-Kendall对降雨量进行突变性检验。分析结果表明:虽然两种方法是从不同时间段对辽西北地区降雨量进行检验,但二者结果基本吻合,整体上辽西北地区降雨量呈下降趋势,且变化比较稳定;辽西北地区虽个别城市在一些年份降雨出现了上升趋势,但整体上还是下降趋势较显著,这与趋势分析结果相似,也与实际情况相符。

关中盆地降水量变化趋势的Mann-Kendall分析

采用关中盆地1959—2006年的气象资料,应用Mann-Kendall检验方法分析了关中盆地降水量的年季变化趋势和突变情况。结果表明:关中盆地降水量总体呈减少趋势;春、秋季节降水量呈下降趋势,夏、冬两季降水量均呈上升趋势;年降水量的突变发生在1992年,之后降水量总体开始下降,到21世纪依旧呈减少趋势;春季降水量在1994年发生突变,降水量明显下降;夏季降水量突变于1978年,之后降水量开始上升;秋季突变于1973年,之后降水量转变为下降趋势;冬季降水量总体呈增加趋势。

Detecting Global Vegetation Changes Using Mann-Kendal(MK) Trend Test for 1982–2015 Time Period

Vegetation is the main component of the terrestrial ecosystem and plays a key role in global climate change. Remotely sensed vegetation indices are widely used to detect vegetation trends at large scales. To understand the trends of vegetation cover, this research examined the spatial-temporal trends of global vegetation by employing the normalized difference vegetation index(NDVI) from the Advanced Very High Resolution Radiometer(AVHRR) Global Inventory Modeling and Mapping Studies(GIMMS) time series(1982–2015). Ten samples were selected to test the temporal trend of NDVI, and the results show that in arid and semi-arid regions, NDVI showed a deceasing trend, while it showed a growing trend in other regions. Mann-Kendal(MK) trend test results indicate that 83.37% of NDVI pixels exhibited positive trends and that only 16.63% showed negative trends(P < 0.05) during the period from 1982 to 2015. The increasing NDVI trends primarily occurred in tree-covered regions because of forest growth and re-growth and also because of vegetation succession after a forest disturbance. The increasing trend of the NDVI in cropland regions was primarily because of the increasing cropland area and the improvement in planting techniques. This research describes the spatial vegetation trends at a global scale over the past 30+ years, especially for different land cover types.

Relationship between Mutation of IR in the mtr System of Neisseria Gonorrhoeae and Multiple Antibiotic Resistance

To study the relationship between mutation of the inverted repeat sequence （IR） in the multiple transferable resistant system （mtr） of Neisseria gonorrhoeae （NG） and its multiple antibiotic resistance, minimal inhibitory concentrations （MICs） for the clinically isolated strains were tested by agar-dilution-method. The mtr system＇s IR gene of NG was sequenced after amplification by polymerase chain reaction （PCR）. Either two susceptive or five penicillin-resistant strains had no base mutation in IR gene, while all of the 13 strains with multiple-antibiotic-resistance had a singlebase deletion （A/T）. The result suggests that a single-base deletion of the thirteen-base IR sequence in mtr system of NG might result in multiple antibiotic resistance but is not associated with single antibiotic resistance.

Mutation Analysis of STR Locus on 23 Autosomes in Hainan Population

[Objective] To analyze the mutation signature and regularity of STR locus on 23 autosomes in paternity testing cases in Hainan. [Methods] A total of 2715 paternity testing cases accepted by the Forensic Medical Identification Centre of our hospital from 2017 to 2020 derived from counties and cities in Hainan Province were collected, the cases containing gene mutations were selected, the mutation rate and details of each locus were counted, and the mutation regu-larity of 23 STR loci was analyzed. [Results] Of the 2715 cases identified as “support”, 1487 were triplet cases and 1640 were dyad cases, totaling 4614 meioses;There were 50 gene mutation events (including 17 triplet mutations and 33 dyad mutations), with an average mutation rate of 0.0047% and a cumulative mutation rate of 1.0837%. A total of 19 of the 23 STR loci were mutated, with a mutation rate of 0.1301% at the D12S391 locus and 0.0217% at five loci, TPOX, D1S1656, D2S441, D22S1045, and PentaD, while no muta-tion events were found at four loci, D19S433, TH01, D13S317, and D7S820. Of the 50 mutation events, 47 were one-step mutations, 1 was two-step, and 2 were three-step. There were 35 paternal mutations (13 triplets and 22 dyads), 6 maternal mutations (4 triplets and 2 dyads), and 9 indeterminate pater-nal/maternal mutations, with a paternal to maternal mutation ratio of 5.83:1. [Conclusion] The mutation rate of D12S391 locus is the highest, and the muta-tion rate of TPOX, D1S1656, D2S441, D22S1045 and PentaD loci is the lowest in Hainan population, and paternal mutations are more than maternal muta-tions. In the paternity test, if 1 - 3 STR loci do not conform to the genetic law, especially when the mutant locus is homozygous or the next of kin is identi-fied, it is necessary to use other kits to review and increase the number of loci or use the second-generation sequencing technology to confirm, carefully de-termine the mutation and ensure the accuracy of the identification conclusion.

Establishment and application of a multiplex genetic mutation-detection method of lung cancer based on MassARRAY platform

Objective: This study aims to establish a method for highly parallel multiplexed detection of genetic mutations in Chinese lung cancer samples through Agena i PLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on Mass ARRAY mass spectrometry platform.Methods: We reviewed the related literature and data on lung cancer treatments. We also identified 99 mutation hot spots in 13 target genes closely related to the pathogenesis, drug resistance, and metastasis of lung cancer. A total of 297 primers, composed of99 paired forward and reverse amplification primers and 99 matched extension primers, were designed using Assay Design software. The detection method was established by analyzing eight cell lines and six lung cancer specimens. The proposed method was then validated through comparisons by using a Lung Carta^(TM) kit. The sensitivity and specificity of the proposed method were evaluated by directly sequencing EGFR and KRAS genes in 100 lung cancer cases.Results: The proposed method was able to detect multiplex genetic mutations in lung cancer cell lines. This finding was consistent with the observations on previously reported mutations. The proposed method can also detect such mutations in clinical lung cancer specimens. This result was consistent with the observations with Lung Carta^(TM) kit. However, an FGFR2 mutation was detected only through the proposed method. The measured sensitivity and specificity were 100% and 96.3%, respectively.Conclusions: The proposed Mass ARRAY technology-based multiplex method can detect genetic mutations in Chinese lung cancer patients. Therefore, the proposed method can be applied to detect mutations in other cancer tissues.

Mann-Kendall检验法分析降水量时程变化特征

采用金华站1961-2013年逐月降水量资料,运用线性回归分析、累计距平分析以及Mann-Kend-all趋势检验与突变检验分析综合研究了该地区多年降水量的时程变化特征。结果表明:金华站多年降水量整体呈现上升趋势,上升趋势不明显。降水量的季节性差异较大,夏季与冬季表现出较为明显的上升趋势,且夏季降水量上升趋势显著。春季与秋季降水量呈现下降趋势,下降趋势不显著;从整体与季节的分析发现降水量发生突变都集中在20世纪80年代后半段与90年代初。通过对该地区降水量的时程变化特征研究,为该地区的洪涝灾害防治工作提供参考依据。

ACE gene missense mutation in a case with early-onset, rapid progressing dementia

The population of early-onset Alzheimer's disease(EOAD)accounts for 1%-2%of the total population of Alzheimer's disease,and genetic mutations are more common in EOAD.The first symptom of the patient in the present case report was the decline in memories of recent events,and the disease progressed rapidly in the following 2 years.Genetic testing has revealed the presence of genetic mutations(c.A479G,p.N160S)of ACE,which causes the 160th codon of the ACE protein to change from aspartic acid to serine,and at the same time genotype of apolipoprotein E(APOE)is ε3/ε4.We think that this patient carries the mutation type of the sensitive gene ACE and the risk gene APOE of Alzheimer's disease,and this is the reason why the disease progressed rapidly.Moreover,we discussed ACE genetic mutation's meaning in EOAD progression.

New real-time-PCR method to identify single point mutations in hepatitis C virus

AIM To develop a fast, low-cost diagnostic strategy to identify single point mutations in highly variable genomes such as hepatitis C virus(HCV).METHODS In patients with HCV infection, resistance-associated amino acid substitutions within the viral quasispecies prior to therapy can confer decreased susceptibility to direct-acting antiviral agents and lead to treatment failure and virological relapse. One such naturally occurring mutation is the Q80 K substitution in the HCV-NS3 protease gene, which confers resistance to PI inhibitors, particularly simeprevir. Low-cost, highly sensitive techniques enabling routine detection of these single point mutations would be useful to identify patients at a risk of treatment failure. Light Cycler methods, based on real-time PCR with sequencespecific probe hybridization, have been implemented in most diagnostic laboratories. However, this technique cannot identify single point mutations in highly variable genetic environments, such as the HCV genome. To circumvent this problem, we developed a new method to homogenize all nucleotides present in a region except the point mutation of interest. RESULTS Using nucleotide-specific probes Q, K, and R substitutions at position 80 were clearly identified at a sensitivity of 10%(mutations present at a frequency of at least 10% were detected). The technique was successfully applied to identify the Q80 K substitution in 240 HCV G1 serum samples, with performance comparable to that of direct Sanger sequencing, the current standard procedure for this purpose. The new method was then validated in a Catalonian population of 202 HCV G1-infected individuals. Q80 K was detected in 14.6% of G1 a patients and 0% of G1 b in our setting. CONCLUSION A fast, low-cost diagnostic strategy based on real-time PCR and fluorescence resonance energy transfer probe melting curve analysis has been successfully developed to identify single point mutations in highly variable genomes such as hepatitis C virus. This technique can be adapted to detect any single point mutation in highly variable genomes.

基于Mann-Kendall突变检验与ARIMA模型的臭氧水平预测

目的针对未来50年臭氧水平预测,首先以南半球为例,从美国航空航天局(NASA)中获取1985—2015年臭氧含量的数据,按季节分为4类。方法运用Mann-Kendall突变检验的方法,利用MATLAB软件对数据进行检验,应用ARIMA模型对不同季节分别进行预测,考虑到影响大气中臭氧含量的3类因素:相关卤烃浓度、氟氯烃浓度以及氮氧化物浓度,以它们为自变量,臭氧含量为因变量做多元线性回归模型。结果全球30年的春季未出现大的突变,全球30年夏季未出现大的突变,全球30年秋季未出现大的突变,全球30年冬季未出现大的突变;其次,残差序列已经可以认为是一个纯白噪声的序列。结论未来50年臭氧含量不会一直减少,因变量与自变量成反比,即这些物质的排放量逐渐减少,未来50年大气中的臭氧含量缓慢升高至平稳。

凤阳近61年干燥指数变化的Mann-Kendall检验

采用凤阳站1957-2017年气象资料,构建近61年干燥指数时间序列,运用时间因子直线回归、Mann-Kendall趋势检验与突变分析综合研究了该地区多年干燥指数的时程变化特征。结果表明:凤阳多年干燥指数整体呈现下降趋势,没有突变现象,其中1987年、1989-2017年趋势检验统计量达到显著水平。历年干燥指数最大、最小值分别出现在1978年、1991年。干燥指数在总体下降的趋势中,表现出较大的年际波动,旱涝容易发生。通过对凤阳干燥指数时程变化特征研究,为该地区的防汛抗旱工作提供参考依据。

A Novel Gene Mutation of Runx2 in Cleidocranial Dysplasia

Haploinsufficiency of the runt-related transcription factor 2（Runx2） gene is widely known to be responsible for cleidocranial dysplasia（CCD）. To date, more than 190 mutations in Runx2 gene have been reported to be related to CCD. In this study, a novel mutation of Runx2 gene was observed in a female with CCD. Genomic DNA was extracted from peripheral venous blood of the proband and eleven members of her family. Genetic testing on these twelve people identified a novel missense mutation（c.895 T〉C, Y299 H） in exon 5 of the RUNX2 gene in the proband. This mutation results in an amino acid change at codon 895（P.Tyr 299 His.） from a tryptophan codon（TAT） to a histidine codon（CAT）. Our finding may further extend the known mutation spectrum of the RUNX2 gene, and facilitate prenatal genetic diagnosis of CCD in the future.