Accurate prediction of BRCA1 and BRCA2 heterozygous genotype using expression profiling after induced DNA damage.

PURPOSE: In this study, the differential gene expression changes following radiation-induced DNA damage in healthy cells from BRCA1/BRCA1 mutation carriers have been compared with controls using high-density microarray technology. We aimed to establish if BRCA1/BRCA2 mutation carriers could be distinguished from noncarriers based on expression profiling of normal cells. EXPERIMENTAL DESIGN: Short-term primary fibroblast cultures were established from skin biopsies from 10 BRCA1 and 10 BRCA2 mutation carriers and 10 controls, all of whom had previously had breast cancer. The cells were subjected to 15 Gy ionizing irradiation to induce DNA damage. RNA was extracted from all cell cultures, preirradiation and at 1 hour postirradiation. For expression profiling, 15 K spotted cDNA microarrays manufactured by the Cancer Research UK DNA Microarray Facility were used. Statistical feature selection was used with a support vector machine (SVM) classifier to determine the best feature set for predicting BRCA1 or BRCA2 heterozygous genotype. To investigate prediction accuracy, a nonprobabilistic classifier (SVM) and a probabilistic Gaussian process classifier were used. RESULTS: In the task of distinguishing BRCA1 and BRCA2 mutation carriers from noncarriers and from each other following radiation-induced DNA damage, the SVM achieved 90%, and the Gaussian process classifier achieved 100% accuracy. This effect could not be achieved without irradiation. In addition, the SVM identified a set of BRCA genotype predictor genes. CONCLUSIONS: We conclude that after irradiation-induced DNA damage, BRCA1 and BRCA2 mutation carrier cells have a distinctive expression phenotype, and this may have a future role in predicting genotypes, with application to clinical detection and classification of mutations.     

Computer use and carpal tunnel syndrome: a 1-year follow-up study

Context  Computer use is increasingly common among many working populations, and concern exists about possible adverse effects of computer use, such as carpal tunnel syndrome (CTS). Objectives  To estimate the prevalence and incidence of possible CTS and to evaluate the contribution of use of mouse devices and keyboards to the risk of possible CTS. Design and Setting  A 1-year follow-up study with questionnaires conducted in 2000 and 2001 at 3500 workplaces in Denmark, followed on each of the 2 occasions by a clinical interview on symptom distribution and frequency. Participants  The questionnaire was sent to 9480 members of a trade union, with an initial response rate of 73% (n = 6943), and 82% (n = 5658) at follow-up. Main Outcome Measures  At baseline, there were 3 outcome measures: tingling/numbness in the right hand once a week or more as reported in the questionnaire; tingling, numbness, and pain in the median nerve in the right hand confirmed by clinical interview; and tingling, numbness, and pain in the median nerve in the right hand at night confirmed by clinical interview. At 1 year of follow-up the main outcome of interest was onset of symptoms among participants who had no or minor symptoms at baseline. Results  The overall self-reported prevalence of tingling/numbness in the right hand at baseline was 10.9%. The interview confirmed that prevalence of tingling/numbness in the median nerve was 4.8%, of which about one third, corresponding to a prevalence of 1.4%, experienced symptoms at night. Onset of new symptoms in the 1-year follow-up was 5.5%. In the cross-sectional comparisons and in the follow-up analyses, there was an association between use of a mouse device for more than 20 h/wk and risk of possible CTS but no statistically significant association with keyboard use. Conclusions  The occurrence of possible CTS in the right hand was low. The study emphasizes that computer use does not pose a severe occupational hazard for developing symptoms of CTS.      

Infant feeding in the second 6 months of life related to iron status: an observational study.

OBJECTIVE: To investigate the relationship between iron status in infancy and type of milk and weaning solids consumed. DESIGN: An observational cohort study. SETTING: 928 term infants from the Avon Longitudinal Study of Parents and Children in 1993-94. METHODS: Haemoglobin and ferritin concentrations at 8 and 12 months were assessed in relation to type and quantity of milk intake at 8 months. RESULTS: By WHO criteria, 22.7% of the infants were anaemic at 8 months and 18.1% at 12 months. More breast--than formula-fed infants were anaemic at 8 and 12 months. Cows' milk as the main drink was associated with increased anaemia at 12 months and low ferritin at 8 and 12 months. No association was found between any nutrients and haemoglobin concentrations. Protein and non-haem iron intakes were positively associated with ferritin concentrations and calcium intake negatively. This effect was more marked in infants being fed cows' milk. More than 25% of infants in the breast milk and cows' milk groups and 41% of infants having >6 breast feeds per day had iron intakes below the lower reference nutrient intake. Feeding cows' milk or formula above 600 ml or >6 breast feeds per day was associated with lower intakes of solids. CONCLUSIONS: Both breast and cows' milk feeding were associated with higher levels of anaemia. Satisfactory iron intake from solids in later infancy is more likely if formula intake is <600 ml per day and breast feeds are limited to <6 feeds per day. Cows' milk should be strongly discouraged as a main drink before 12 months.     

Some notions and units in radioepidemiology and radiation protection

Summary An annotated list of some notions and units used in radioepidemiology is presented, with special emphasis on differentiating between the realms of radiation physics, radiation biology, radioepidemiology and radiation protection.

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Begriffe und Einheiten in Strahlenbiologie,-epidemiologie und-schutz

Zusammenfassung Diese kommentierte Liste einiger Begriffe und Masszahlen soll das Sich-Einlesen in Arbeiten aus Strahlenepidemiologie und Strahlenschutz erleichtern, indem Bedeutung und Begriffsbereich der verwendeten Begriffe aus den Disziplinen Strahlenphysik,-biologie,-epidemiologie und-schutz kurz charakterisiert werden.

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Quelques concepts et unités utilisés en radioépidémiologie et dans la radio-protection

Résumé Cet article présente une liste commentée de quelques concepts et unités d'usage courant en radioépidémiologie; une attention particulière est accordée au sens propre des termes dans les disciplines concernées, telles la physique des radiations, la biologie des radiations, la radio-épidémiologie, la protection contre les radiations.

     

验证治疗措施的公平——高质量研究促进高质量卫生保健（Ⅶ）

第6章 精简、优质且出于正当理由的研究 多年前，《英国医学杂志》（BMJ）刊登的一篇社论标题醒目：“低质量医学研究的丑闻”。作者提倡精简、优质且出于正当理由的研究。前几章已经提到了困扰该作者的一些问题。     

验证治疗措施的公平——高质量研究促进高质量卫生保健（Ⅷ）

第7章 进一步验证治疗措施是每个人的职责 前几章已经讨论了开展低质量的或不必要的治疗措施效果研究会浪费掉多少时间、金钱和精力，这些研究现在不能，将来也无法解决与患者相关的问题。同时也总结了妨碍我们解决治疗性研究中不可避免的不确定性的一些因素.     

The impact of donor body mass index on outcomes after deceased kidney transplantation – a national population‐cohort study

The aim of this study was to determine the effect of donor body mass index (BMI) on deceased donor kidney transplant outcomes. Data were collected from the UK Transplant Registry for all deceased donor kidney transplant recipients between January 2003 and January 2015. Univariable and multivariable analyses were undertaken to assess the impact of donor BMI on a range of outcomes. Donor BMI (kg/m²) was stratified as <18.5 (n = 380), 18.5–25.0 (n = 6890), 25.1–30.0 (n = 6669), 30.1–35.0 (n = 2503) and >35.0 (n = 1148). The prevalence of delayed graft function increased significantly with donor BMI (P < 0.001), with an adjusted odds ratio of 1.38 (95% CI: 1.16–1.63) for the >35.0 vs. 18.5–25.0 groups. However, there was no significant association between donor BMI and 12‐month creatinine (P = 0.550), or patient (P = 0.109) or graft (P = 0.590) survival. In overweight patients, increasing donor BMI was associated with a significant increase in warm ischaemia time and functional warm ischaemia time, by an average of 4.6% (P = 0.043) and 5.2% (P = 0.013) per 10.0 kg/m². However, rising warm ischaemic time and functional warm ischaemic time was not significantly associated with delayed graft function, 12‐month creatinine levels, graft loss or patient death. In this population cohort study, we identified no significant association between donor BMI and long‐term clinical outcomes in deceased donor kidney transplantation.     

验证治疗措施的公平——高质量研究促进高质量卫生保健(IV)

第三章公平试验的主要概念 前两章介绍了未充分验证的治疗措施可能造成严重危害.显然,严格评价治疗措施对于确定是否应将治疗措施用于患者是非常重要的.