Cox模型中基于Model-X Knockoffs的高维控制变量选择方法

在生物医学、临床试验和流行病学等领域的研究中,由于获得生存数据的试验设计、观测时间的局限,以及观测对象在进入或退出试验时的个体差异等方面的原因,与所关注事件的发生时间相关的数据经常存在右删失。基于右删失生存数据解析协变量和生存时间的关系时,应用最为广泛的统计模型是Cox模型。随着科学技术的进步,数据收集变得越来越容易,导致数据库规模越来越大、复杂性越来越高,数据的维度通常可以达到成百上千维,甚至更高。文章提出一种Cox模型中基于Model-X Knockoffs的高维控制变量选择方法。首先基于Knockoffs框架建立一个Knockoffs变量,并基于原始协变量和其相应的Knockoffs变量构造一个正则化的目标函数,然后通过求解目标函数的最优解构造一个统计量和基于数据的阈值,最后进行变量选择。模拟分析和实证研究结果表明:所提方法可以在变量选择的同时提供可靠的FDR控制,优于传统的LASSO方法。

Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

Modelling the viscoplastic behaviour of Callovo-Oxfordian claystone with consideration of damage effect

In order to evaluate the performance of deep geological disposal of radioactive waste,an underground research laboratory(URL)was constructed by Andra in the Callovo-Oxfordian(COx)claystone formation at the Meuse/Haute-Marne(MHM).The construction of URL induced the excavation damage of host formations,and the ventilation in the galleries desaturated the host formation close to the gallery wall.Moreover,it is expected that the mechanical behaviour of COx claystone is time-dependent.This study presents a constitutive model developed to describe the viscoplastic behaviour of unsaturated and damaged COx claystone.In this model,the unsaturation effect is considered by adopting the Bishop effective stress and the van Genuchten(VG)water retention model.In terms of the viscoplastic behaviour,the nonstationary flow surface(NSFS)theory for unsaturated soils is used with consideration of the coupled effects of strain rate and suction on the yield stress.A progressive hardening law is adopted.Meanwhile,a non-associated flow rule is used,which is similar to that in Barcelona basic model(BBM).In addition,to describe the damage effect induced by suction change and viscoplastic loading,a damage function is defined based on the crack volume proportion.This damage function contains two variables:unsaturated effective stress and viscoplastic volumetric strain,with the related parameters determined based on the mercury intrusion porosimetry(MIP)tests.For the model validation,different tests on COx claystone under different loading paths are simulated.Comparisons between experimental and simulated results indicated that the present model is able to well describe the viscoplastic behaviour of damaged COx claystone,including swelling/shrinkage,triaxial extension and compression,and triaxial creep.

Evaluating the role of large language models in inflammatory bowel disease patient information

This letter evaluates the article by Gravina et al on ChatGPT’s potential in providing medical information for inflammatory bowel disease patients.While promising,it highlights the need for advanced techniques like reasoning+action and retrieval-augmented generation to improve accuracy and reliability.Emphasizing that simple question and answer testing is insufficient,it calls for more nuanced evaluation methods to truly gauge large language models’capabilities in clinical applications.

基于Lasso-Cox回归模型的肺腺癌基因学预后风险分析

目的通过构建Lasso-Cox模型筛选肺腺癌差异表达基因,计算患者风险评分,构建肺腺癌预测模型,为肺腺癌的研究提供潜在的基因靶点,并为临床诊疗及预后提供新方向。方法下载癌症基因组图谱(TCGA)和肿瘤基因表达数据库(GEO)的肺腺癌基因表达和临床数据,用TCGA数据库训练模型,并合并两数据库用以模型验证,筛选的肺腺癌差异表达基因(DEGs)通过多因素Lasso-Cox回归构建风险评分预后模型,结合临床资料以确定肺腺癌最终的独立预后预测因素。利用GO富集分析、KEGG通路分析和CIBERSORTx免疫分析对风险模型差异表达基因进行生物学解释。结果通过单变量Cox和Lasso-Cox回归分析,获得了与肺腺癌预后相关的9个差异表达基因。结合临床数据的多因素Cox回归模型显示,恶性肿瘤病史、N分期、T分期和风险评分是预后的独立影响因素。结论本研究构建的肺腺癌预后模型可以有效预测患者的预后风险,为临床决策和个性化治疗提供理论基础。

Solving the Olbers’s Paradox, Explaining the “Red-Shift”, and Challenging the Relativities by “Sun Matters Theory” and “Sun Model of Universe”, an Evolution of the Einstein’s Static Universe Model

Olbers’s paradox, known as the dark night paradox, is an argument in astrophysics that the darkness of the night sky conflicts with the assumption of an infinite and eternal static universe. Big-Bang theory was used to partially explain this paradox, while introducing new problems. Hereby, we propose a better theory, named Sun Matters Theory, to explain this paradox. Moreover, this unique theory supports and extended the Einstein’s static universe model proposed by Albert Einstein in 1917. Further, we proposed our new universe model, “Sun Model of Universe”. Based on the new model and novel theory, we generated innovative field equation by upgrading Einstein’s Field Equation through adding back the cosmological constant, introducing a new variable and modifying the gravitationally-related concepts. According to the Sun Model of Universe, the dark matter and dark energy comprise the so-called “Sun Matters”. The observed phenomenon like the red shift is explained as due to the interaction of ordinary light with Sun Matters leading to its energy and frequency decrease. In Sun Model, our big universe consists of many universes with ordinary matter at the core mixed and surrounded with the Sun Matters. In those universes, the laws of physics may be completely or partially different from that of our ordinary universe with parallel civilizations. The darkness of night can be easily explained as resulting from the interaction of light with the Sun Matters leading to the sharp decrease in the light intensity. Sun Matters also scatter the light from a star, which makes it shining as observed by Hubble. Further, there is a kind of Sun Matters named “Sun Waters”, surrounding every starts. When lights pass by the sun, the Sun Waters deflect the lights to bend the light path. According to the Sun Model, it is the light bent not the space bent that was proposed in the theory of relativities.

Hubble Tension Explanation from This Cosmological Model AΛΩ (Slow Bang Model, SB)

In this article we present a model of Hubble-Lemaître law using the notions of a transmitter (galaxy) and a receiver (MW) coupled to a model of the universe (Slow Bang Model, SB), based on a quantum approach of the evolution of space-time as well as an equation of state that retains all the infinitesimal terms. We find an explanation of the Hubble tension H0. Indeed, we have seen that this constant depends on the transceiver pair which can vary from the lowest observable value, from photons of the CMB (theoretical [km/s/Mpc]) to increasingly higher values depending on the earlier origin of the formation of the observed galaxy or cluster (ETG ~0.3 [Gy], ~74 [km/s/Mpc]). We have produced a theoretical table of the values of the constant according to the possible pairs of transmitter/receiver in the case where these galaxies follow the Hubble flow without large disturbance. The calculated theoretical values of the constant are in the order of magnitude of all values mentioned in past studies. Subsequently, we applied the models to 9 galaxies and COMA cluster and found that the models predict acceptable values of their distances and Hubble constant since these galaxies mainly follow the Hubble flow rather than the effects of a galaxy cluster or a group of clusters. In conclusion, we affirm that this Hubble tension does not really exist and it is rather the understanding of the meaning of this constant that is questioned.

Analysis of Porter’s Five Forces Competitive Model in China’s Property Rights Trading Market

In recent years,China’s property rights trading market has been extremely competitive,but there are also new contradictions and challenges.This paper aims to analyze the external and internal competitive market of the property rights market through Porter’s five forces competition model,then find out the problems and defects in the development,thereby promoting the better development and progress of China’s property rights trading market.

Modelling the Survival of Western Honey Bee Apis mellifera and the African Stingless Bee Meliponula ferruginea Using Semiparametric Marginal Proportional Hazards Mixture Cure Model

Classical survival analysis assumes all subjects will experience the event of interest, but in some cases, a portion of the population may never encounter the event. These survival methods further assume independent survival times, which is not valid for honey bees, which live in nests. The study introduces a semi-parametric marginal proportional hazards mixture cure (PHMC) model with exchangeable correlation structure, using generalized estimating equations for survival data analysis. The model was tested on clustered right-censored bees survival data with a cured fraction, where two bee species were subjected to different entomopathogens to test the effect of the entomopathogens on the survival of the bee species. The Expectation-Solution algorithm is used to estimate the parameters. The study notes a weak positive association between cure statuses (ρ1=0.0007) and survival times for uncured bees (ρ2=0.0890), emphasizing their importance. The odds of being uncured for A. mellifera is higher than the odds for species M. ferruginea. The bee species, A. mellifera are more susceptible to entomopathogens icipe 7, icipe 20, and icipe 69. The Cox-Snell residuals show that the proposed semiparametric PH model generally fits the data well as compared to model that assume independent correlation structure. Thus, the semi parametric marginal proportional hazards mixture cure is parsimonious model for correlated bees survival data.

基于贝叶斯Cox风险比例回归的兰州市HIV感染者/AIDS患者死亡影响因素分析

[目的]了解兰州市HIV/AIDS报告病例相关特征的构成情况,分析艾滋病相关死亡的影响因素。[方法]通过收集兰州市2011-2019年HIV/AIDS报告病例信息,采用生存分析方法,构建贝叶斯Cox风险比例回归模型分析影响死亡的相关因素。[结果]本研究共选取2312例HIV/AIDS患者,其中艾滋病相关死亡45例。多因素回归结果显示,患者年龄越大,死亡风险越高;确诊时为AIDS患者的死亡风险是HIV感染者的13.91倍;与未接受CD4检测的患者相比,接受CD4检测的患者的死亡风险降低;进行抗病毒治疗者的死亡风险是未进行抗病毒治疗者的0.22倍。[结论]确诊时年龄、病程阶段、是否接受抗病毒治疗是兰州市HIV/AIDS患者艾滋病相关死亡的影响因素,因此要加强艾滋病相关人群健康教育,提倡早发现、早诊断、早治疗,扩大艾滋病检测与治疗的覆盖面,延长艾滋病患者的生存时间。

糖尿病肾脏疾病预后影响因素的COX比例风险回归模型分析

目的基于COX比例风险回归模型分析糖尿病肾脏疾病(diabetic kidney disease,DKD)预后的影响因素,为临床早期评估和防治DKD提供科学的依据。方法收集多中心(河南中医药大学第一附属医院、河南中医药大学第三附属医院、河南省中医院及郑州市人民医院)2010—2021年就诊治疗的DKD患者资料,包括一般资料、实验室指标、中医辨证分型及中医药治疗,以肾小球滤过率(eGFR)下降≥50%、血肌酐(Scr)翻倍、DKD 5期、死亡为结局指标,随访其发生时间及情况,利用COX比例风险回归模型分析筛选DKD预后影响因素。结果本研究最终纳入1947例患者,随访时间为4.65(4.557~4.746)年,发生复合终点事件305例(15.67%)。单因素COX回归分析结果表明,不同年龄、DKD病程≥4年、饮酒史、吸烟史、高血压、冠心病、脑血管病、糖尿病足、糖尿病眼病、糖化血红蛋白(HbA1c)、血尿酸(SUA)、Scr、24 h尿蛋白定量(24 h-UTP)、eGFR、湿热血瘀证、脾肾气虚兼湿聚血瘀证、脾肾阳虚兼血瘀证、中药熏洗、服用中药患者DKD预后情况比较,差异有统计学意义(P<0.05)。多因素COX回归分析结果表明,年龄[HR(95%CI)=2.52(1.92,3.30)]、DKD病程[HR(95%CI)=1.62(1.09,2.42)]、吸烟史[HR(95%CI)=1.61(1.13,2.29)]、饮酒史[HR(95%CI)=1.41(1.01,1.95)]、脑血管病[HR(95%CI)=1.33(1.01,1.75)]、糖尿病眼病[HR(95%CI)=1.43(1.13,1.82)]、SUA[HR(95%CI)=1.72(1.26,2.33)]、24 h-UTP[HR(95%CI)=1.48(1.14,1.91)]、脾肾气虚兼湿聚血瘀证[HR(95%CI)=2.22(1.44,3.43)]与DKD发生终点事件的风险关系密切(P<0.05),服用中药[HR(95%CI)=2.57(2.00,3.31)]能够减少终点事件的发生(P<0.05)。结论年龄、DKD病程、吸烟史、饮酒史、脑血管病、糖尿病眼病、SUA、24 h-UTP、脾肾气虚兼湿聚血瘀证是影响DKD患者预后的危险因素,而服用中药治疗为其保护因素。

高压管汇材料疲劳性能测试及P-S-N模型曲线的拟合

高压管汇作为压裂设备中的主要易损件之一,其失效危害较大。它的失效原因主要是疲劳、冲蚀、腐蚀或者材料缺陷引起的刺漏和爆裂,其中尤以疲劳失效最不可预估。目前,对于高压管汇材料的疲劳性能研究不够深入,为解决高压管汇材料疲劳寿命的准确描述问题,以某国产高压管汇材料为例,进行了一系列疲劳试验,并基于试验数据,采用多种分布模型和不同S-N模型进行拟合分析,得出综合评价拟合能力最强的P-S-N模型。结果表明,该材料在中长疲劳寿命区,Weibull三参数模型在7级应力水平下综合评价能力最好;在存活率分别为50%、90%、99%、99.9%时,指数S-N模型的拟合系数均大于0.98,拟合能力最好。得出的P-S-N模型曲线可以为高压管汇的疲劳寿命以及安全设计提供依据。

基于Cox健康行为互动模式的护理措施在宫颈癌患者护理中的应用

目的探讨基于Cox健康行为互动模式的护理措施在宫颈癌患者护理中的应用效果。方法选择2022年3月至2023年3月新乡医学院第一附属医院收治的96例宫颈癌术后患者作为研究对象,按随机数表法将患者分为对照组和观察组各48例。对照组患者术后采用常规护理,观察组患者在对照组护理的基础上给予基于Cox健康行为互动模式的护理措施,两组患者均接受护理至出院,出院后均随访3周。护理结束后出院时,比较两组患者的术后恢复情况(手术切口愈合时间、留置导尿管时间、住院时间)以及护理前、护理后T淋巴细胞亚群中CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平;随访3周回院复查时,比较两组患者的生活质量量表(SF-36)评分;护理结束后出院时,比较两组患者对护理工作的满意度。结果观察组患者的手术切口愈合时间、住院时间、留置导尿管时间分别为(7.60±1.39)d、(1.50±0.24)周、(17.78±2.11)d,明显短于对照组的(10.55±1.51)d、(2.54±0.30)周、(20.10±2.32)d,差异均有统计学意义(P<0.05);观察组患者护理后的CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)水平分别为(70.64±11.67)%、(39.91±5.23)%、1.50±0.27,明显高于对照组的(66.25±11.32)%、(35.21±5.08)%、1.24±0.18,差异均有统计学意义(P<0.05);随访3周回院复查时,观察组患者的家庭生活、精神活力、社交能力、心理承受评分分别为(36.14±1.58)分、(36.02±1.57)分、(37.10±2.55)分、(36.26±2.31)分,明显高于对照组的(32.31±1.62)分、(30.15±1.63)分、(32.19±2.40)分、(33.11±2.14)分,差异均有统计学意义(P<0.05);观察组患者对护理工作的满意度为95.83%,明显高于对照组的83.33%,差异有统计学意义(P<0.05)。结论基于Cox健康行为互动模式的护理措施在宫颈癌患者术后护理中的应用效果良好,能促进患者术后恢复,提高免疫功能和生活质量。

深水采油树Spring-Seal密封圈接触模型构建与实验测试

为提高深水采油树在高压、高温、低温等工况下长时间工作的稳定性,对采油树密封圈进行重新设计,提出Spring-Seal密封圈(以下简称S密封圈);基于赫兹接触理论、填料密封接触理论,重新构建S密封圈接触力学模型;建立有限元仿真分析模型,分析不同条件下S密封圈的密封性能,同时验证新建接触模型的合理性;利用实验测试S密封圈的实际密封效果。研究结果表明:S密封圈在高压、高温、低温等工况下能够长时间稳定工作且密封性能良好。研究结果可为S密封圈的接触研究及工程运用提供理论参考。

D-S理论和Markov链组合的桥梁性能退化预测研究

为准确预测桥梁性能退化,考虑到数据随机性和微小扰动发生状态跳跃,提出了一种D-S(Dempster-Shafer)证据理论和Markov链组合的桥梁性能退化组合预测模型和性能退化率的概念.该模型基于指数平滑(exponential smoothing,ES)方法获得新的预测数据序列,并利用Markov链和D-S理论不断进行优化,从而实现桥梁性能退化的组合预测.实际工程的应用结果表明:性能退化率可以直观地表征在梁性能退化的速度.其次,该模型的平均相对误差为1.54%,较于回归、灰色和模糊加权Markov链模型,精度分别提高了1.11%,0.88%和2.8%,而后验差比值为0.242,小于0.35;模型的标准差为9.021,相比其他模型分别减小了3.978,3.405和7.500,而变异系数为0.109,均小于其他模型,验证了组合预测模型在精度和稳定性方面的优越性,可为在役桥梁结构性能退化预测与维护提供理论基础.

基于量子衍生涡流算法和T⁃S模糊推理模型的储层岩性识别

鉴于梯度下降法易陷入局部极值、普通群智能优化算法易早熟收敛,提出一种基于量子衍生涡流算法(Quantum Vortex Search Algorithm,QVSA)和T⁃S模糊推理模型的岩性识别方法,QVSA具有操作简单、收敛速度快、寻优能力强等优点,有助于T⁃S模糊推理模型获得最优参数配置,从而实现储层岩性的准确识别。首先利用具有全局搜索能力的QVSA优化T⁃S模糊推理模型的各种参数;然后利用主成分分析方法降低获取的地震属性维度;再利用优化的T⁃S模糊推理模型识别储层岩性。实验结果表明,利用反映储层特征的8个地震属性识别储层岩性时,所提方法的识别正确率达到92%,比普通BP网络方法高5.1%,同时查准率、查全率、F1分数等指标也较BP网络方法提升明显。

基于S变换模能量分析的直流电缆故障测距

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U-G-S模式下现代大学附属学校建设的路径思考

U-G-S(大学-政府-学校)三方联动是上海师范大学近年来建设现代大学附属学校的主要模式,上海师范大学、各区政府与中小学校高效协同合作,发挥各方优势,主动服务上海市政府建设“五个新城”的城市战略,办老百姓家门口的好学校。大学附属学校分为挂牌学校和新建学校两种类型,研究从内在机制、实践路径和建设成效三个方面对两类学校的变革发展进行深度剖析,以期为大学附属学校建设提供宝贵经验。