The NHS England 100,000 Genomes Project: feasibility and utility of centralised genome sequencing for children with cancer

Background Whole-genome sequencing (WGS) of cancers is becoming an accepted component of oncological care, and NHS England is currently rolling out WGS for all children with cancer. This approach was piloted during the 100,000 genomes (100 K) project. Here we share the experience of the East of England Genomic Medicine Centre (East-GMC), reporting the feasibility and clinical utility of centralised WGS for individual children locally.Methods Non-consecutive children with solid tumours were recruited into the pilot 100 K project at our Genomic Medicine Centre. Variant catalogues were returned for local scrutiny and appraisal at dedicated genomic tumour advisory boards with an emphasis on a detailed exploration of potential clinical value.Results Thirty-six children, representing one-sixth of the national 100 K cohort, were recruited through our Genomic Medicine Centre. The diagnoses encompassed 23 different solid tumour types and WGS provided clinical utility, beyond standard-of-care assays, by refining (2/36) or changing (4/36) diagnoses, providing prognostic information (8/36), defining pathogenic germline mutations (1/36) or revealing novel therapeutic opportunities (8/36).Conclusion Our findings demonstrate the feasibility and clinical value of centralised WGS for children with cancer. WGS offered additional clinical value, especially in diagnostic terms. However, our experience highlights the need for local expertise in scrutinising and clinically interpreting centrally derived variant calls for individual children.Subject terms: Cancer genomics, Cancer genomics     

移植性肿瘤的自然消退与免疫形成的研究

本文对小鼠移植性肿瘤的自然消退与其免疫形成进行观察,结果表明:自然消退的EAC昆明鼠对肿瘤的再次攻击具有强烈的排斥反应。应用化疗药物RS034(Sodium sald.ofbishemisuccinate of 7β-Hydroxycholesterol)治愈的L_(1210) DBA/2小鼠进行肿瘤再次移植时,同样产生对抗作用。而用化疗药物5-Fu治愈的小鼠没有出现免疫排斥反应。     

Individualized norms of optimal fetal growth: fetal growth potential

OBJECTIVE: To demonstrate that individualized optimal fetal growth norms, accounting for physiologic and pathologic determinants of fetal growth, better identify normal and abnormal outcomes of pregnancy than existing methods. METHODS: In a prospective cohort of 38,033 singleton pregnancies, we identified 9,818 women with a completely normal outcome of pregnancy and characterized the physiologic factors affecting birth weight using multivariable regression. We used those physiologic factors to individually predict optimal growth trajectory and its variation, growth potential, for each fetus in the entire cohort. By comparing actual birth weight with growth potential, population, ultrasound, and customized norms, we calculated for each fetus achieved percentiles, by each norm. We then compared proportions of pregnancies classified as normally grown, between 10th and 90th percentile, or aberrantly grown, outside this interval, by growth potential and traditional norms, in 14,229 complicated pregnancies, 1,518 pregnancies with diabetes or hypertensive disorders, and 1,347 pregnancies with neonatal complications. RESULTS: Nineteen physiologic factors, associated with maternal characteristics and early placental function, were identified. Growth potential norms correctly classified significantly more pregnancies than population, ultrasound, or customized norms in complicated pregnancies (26.4% compared with 18.3%, 18.7%, 22.8%, respectively, all P<.05), pregnancies with diabetes or hypertensive disorders (37.3% compared with 23.0%, 28.0%, 34.0%, respectively, all P<.05) and neonatal complications (33.3% compared with 19.7%, 24.9%, 29.8%, respectively, all P<.05). CONCLUSION: Growth potential norms based on the physiologic determinants of birth weight are a better discriminator of aberrations of fetal growth than traditional norms. LEVEL OF EVIDENCE: II.     

Management of jaundice and prevention of severe neonatal hyperbilirubinemia in infants >or=35 weeks gestation

Kernicterus is still occurring but should be largely preventable if health care personnel follow the recommendations listed in this guideline. These recommendations emphasize the importance of universal, systematic assessment of the risk of severe hyperbilirubinemia, lactation support, close follow-up, and prompt intervention when necessary. A systems-based approach to prevent severe neonatal hyperbilirubinemia should be implemented at all birthing facilities and coordinated with continuing ambulatory care. Translational research is needed to better understand the mechanisms of bilirubin neurotoxicity and potential therapeutic interventions.     

人血清催乳素的放射免疫测定

利用本室标记的人催乳素,采用非平衡温育程序,对238例正常成人血液催乳素进行了测定。不同性别、年龄组间未见明显差别,总均值18.9ng/ml,m±2SD范围0.5～37.3 ng/ml。对292例不同病理状态者血样进行了测定,Klinefelter氏综合征Sheehan氏综合征、侏儒症、糖尿病(Ⅰ型及Ⅱ型),续发性闭经、Cushing氏综合征等,血催乳素均在正常范围。男性女乳、甲状腺低功、不孕症、泌乳闭经综合征、垂体瘤等,血液催乳素显著增高。正常人在应激状态时血催乳素亦显著升高。     

妊娠高血压综合征及过期妊娠时胎膜超微结构的观察

报告正常足月产、妊娠高血压综合征及过期妊娠时胎膜在光镜和电镜下的结构及变化特点。观察发现,妊娠高血压综合征时胎膜为缺氧所致的可复性病变,而过期妊娠之胎膜则为不可复性自身老化。胎膜广泛纤维化表明在妊娠高血压综合征和过期妊娠时易发生早破膜。此外,尚讨论了胎膜屏障存在的可能机制及明、暗细胞这一现象。     

圆弧青霉提取物诱发人羊膜细胞程序外DNA合成及合成抑制的研究

从食管癌高发区河南省林县的粮食中,分离出5株圆弧青霉(Penicillium cyclopiumWestling)用大米做培养基,25℃培养两周,经氯仿:甲醇等连续提取后,得到棕褐色膏状提取物。用其中的4株,诱发出了人羊膜FL细胞株的程序外DNA合成(Unscheduled DNA Synthesis,UDS)与DNA合成抑制(DNA Synthesis Inhibition,DSI),与溶剂对照比较,具有显著性差异(P<0.05),并在一定程度上存在剂量效应关系;加S_9后,其生物学活性明显降低,推测此提取物中含有能引起人羊膜细胞DNA损伤的直接诱变剂。     

优秀游泳运动员大运动量训练期间的超声心动图测定

<正> 自1967年Feignbaum首先应用超声心动图测算心搏量以来,发展迅速,目前已广泛用于心脏功能和结构的测定。Morganroth等1975年发表题为“有训练运动员运动性左室肥大”。我国白洁心等于1979年报道了运动员超声心动图的测量分析。近几年来,国内关于运动员的超声心动图已先后发表了二十多篇文章,都是属于一次性的测定,在作横向比较时,由于仪