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Chromosomal instability in cancer consists of dynamic changes to the number and structure of chromosomes1,2. The resulting diversity in somatic copy number alterations (SCNAs) may provide the variation necessary for tumour evolution1,3,4. Here we use multi-sample phasing and SCNA analysis of 1,421 samples from 394 tumours across 22 tumour types to show that continuous chromosomal instability results in pervasive SCNA heterogeneity. Parallel evolutionary events, which cause disruption in the same genes (such as BCL9, MCL1, ARNT (also known as HIF1B), TERT and MYC) within separate subclones, were present in 37% of tumours. Most recurrent losses probably occurred before whole-genome doubling, that was found as a clonal event in 49% of tumours. However, loss of heterozygosity at the human leukocyte antigen (HLA) locus and loss of chromosome 8p to a single haploid copy recurred at substantial subclonal frequencies, even in tumours with whole-genome doubling, indicating ongoing karyotype remodelling. Focal amplifications that affected chromosomes 1q21 (which encompasses BCL9, MCL1 and ARNT), 5p15.33 (TERT), 11q13.3 (CCND1), 19q12 (CCNE1) and 8q24.1 (MYC) were frequently subclonal yet appeared to be clonal within single samples. Analysis of an independent series of 1,024 metastatic samples revealed that 13 focal SCNAs were enriched in metastatic samples, including gains in chromosome 8q24.1 (encompassing MYC) in clear cell renal cell carcinoma and chromosome 11q13.3 (encompassing CCND1) in HER2+ breast cancer. Chromosomal instability may enable the continuous selection of SCNAs, which are established as ordered events that often occur in parallel, throughout tumour evolution.

We prove a new off-diagonal asymptotic of the Bergman kernels associated to tensor powers of a positive line bundle on a compact Kähler manifold. We show that if the Kähler potential is real analytic, then the Bergman kernel accepts a complete asymptotic expansion in a neighborhood of the diagonal of shrinking size 1\14 These improve the earlier results in the subject for smooth potentials, where an expansion exists in a 7kappa; neighborhood of the diagonal. We obtain our results by finding upper bounds of the form Cmm2 for the Bergman coefficients bm(x,) which is an interesting problem on its own. We find such upper bounds using the method of [3]. We also show that sharpening these upper bounds would improve the rate of shrinking neighborhoods of the diagonal x = y in our results. In the special case of metrics with local constant holomorphic sectional curvatures, we obtain off-diagonal asymptotic in a fixed (ask→∞) neighborhood of the diagonal, which recovers a result of Berman [2] (see Remark 3.5 of [2] for higher dimensions). In this case, we also find an explicit formula for the Bergman kernel mod $O(e-kδ) $.

Objective To investigate the influence of video and audio-visual materials based on visual thinking theory on nursing students' professional cognition and emotion, and to find methods to improve nursing students' professional cognition and strengthen positive emotion orientation, so as to provide basis for nursing curriculum reform. Methods The phenomenological method was used to conduct in-depth interviews with 14 nursing students in the school of Nursing of Henan University of science and Technology, and the data were analyzed by Colaizzi's 7-step method analysis method. Results The influence of video and audio-visual materials based on visual thinking theory on nursing students' professional cognition and emotion can be summarized into four themes: Deepening professional cognition; Improving learning enthusiasm; Deepening professional identity and nursing specialty; assertiveness of engaging in nursing specialty. Conclusion Nursing students have shortcomings, such as insufficient professional cognition, low professional learning enthusiasm and weak professional identity. Nursing teachers need to reform nursing courses by establishing video and audio-visual resource database to enhance nursing students' learning enthusiasm and professional identity. (目的 研究基于视觉思维理论的影、视听资料对护理学生的专业认知和情感的影响, 寻求提升护理学生专业认知、强化专业情感的方法, 为护理专业课程改革提供依据。方法 影视、听资料干预后对14名某高校本科护理学生进行深入访谈, 并运用Colaizzi 7步分析法对访谈资料分析。结果 观看影视、听资料后护理学生在专业认知和情感影响的质性资料可以归纳为四个主题: 专业认知加深、学习积极性提升、专业认同感加深、从事护理专业的信心更加坚定。结论 新入校的护理学生存在专业认知不足、学习积极性不高、专业认同感不强等问题, 需要护理教师通过建立有效的教学措施增强护理学生专业认识, 增加专业认同感, 从而提升专业的学习积极性和热爱护理专业。)

Unexplained recurrent spontaneous abortion (URSA) is a major concern in reproductive medicine. Neutrophil cytosolic factor 1 (NCF1) polymorphisms leading to low production of reactive oxygen species (ROS) are strongly associated with autoimmune diseases. We investigated the association of the missense single nucleotide polymorphism (SNP) rs201802880 (NCF1-339) in NCF1 with URSA and explored its function. We performed NCF1-339 SNP genotyping of samples from 152 Chinese patients with URSA and 72 healthy controls using nested PCR and TaqMan assays. ROS production and RELA (NF-κB subunit) expression in the blood of participants with different NCF1-339 genotypes were determined. The frequencies of the wild-type (GG) and mutant (GA) genotypes remarkably differed between the URSA and control groups. The mutant genotype was associated with an increased risk of recurrent abortion. Furthermore, ROS levels in the URSA group with the GG genotype were significantly higher than those in the group with the GA genotype (p < 0.05). RELA expression in URSA patients with the GA genotype was considerably higher than that in control individuals with the GG genotype. These findings indicate that mutations in NCF1 may increase the risk of URSA via the NADP/ROS/NF-κB signaling pathway, which has implications for the diagnosis and treatment of URSA.