Detection of a questing <Emphasis Type="Italic">Hyalomma marginatum</Emphasis><Emphasis Type="Italic">marginatum</Emphasis> adult female (Acari,Ixodidae) in southern Germany

The first finding of a questing Hyalomma marginatum marginatum female tick in Germany is described. The tick was found in May 2006 on the clothing of a person who had spent the preceding day in rural surroundings in southern Germany. As the infested person had also been visiting Spain where H. m. marginatum is known to occur some weeks prior to finding the tick, it is not clear whether the tick had been imported by him as a female or by another host in a preimaginal stage and succeeded to develop to an adult in Germany. H. m. marginatum is a thermophilic tick species usually occurring in relatively dry and warm regions of southern Europe, northern Africa and some parts of Asia. It is a vector of several disease agents of human relevance including Crimean-Congo hemorrhagic fever virus. Although, by PCR examination, the female was found neither infected with this virus nor with Rickettsia aeschlimannii, another human pathogen which has been found in Spanish Hyalomma ticks, its mere finding should be taken seriously and draw further attention to the increasing problem of the import and spread of putatively tropical vectors of disease to central Europe.     

Colorectal cancer ascertainment through cancer registries,hospital episode statistics,and self-reporting compared to confirmation by clinician: A cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

BackgroundElectronic health records are frequently used for cancer epidemiology. We report on their quality for ascertaining colorectal cancer (CRC) in UK women.MethodsPopulation-based, retrospective cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Postmenopausal women aged 50–74 who were diagnosed with CRC during 2001–11 following randomisation to the UKCTOCS were identified and their diagnosis confirmed with their treating clinician. The sensitivity and positive predictive value (PPV) of cancer and death registries, hospital episode statistics, and self-reporting were calculated by pairwise comparisons to the treating clinician’s confirmation, while specificity and negative predictive value were estimated relative to expected cases.ResultsNotification of CRC events were received for 1,085 women as of 24 May 2011. Responses were received from 61% (660/1,085) of clinicians contacted. Nineteen women were excluded (18 no diagnosis date, one diagnosed after cut-off). Of the 641 eligible, 514 had CRC, 24 had a benign polyp, and 103 had neither diagnosis. The sensitivity of cancer registrations at one- and six-years post-diagnosis was 92 (95% CI 90–94) and 99% (97–100), respectively, with a PPV of 95% (95% CI 92/93–97). The sensitivity & PPV of cancer registrations (at one-year post-diagnosis) & hospital episode statistics combined were 98 (96–99) and 92% (89–94), respectively.ConclusionsCancer and death registrations in the UK are a reliable resource for CRC ascertainment in women. Hospital episode statistics can supplement delays in cancer registration. Self-reporting seems less reliable.     

Prediction value of intercellular adhesion molecule-1 gene polymorphisms for epithelial ovarian cancer risk,clinical features,and prognosis

Intercellular adhesion molecule-1 (ICAM-1, encoded by ICAM-1) is implicated in tumorigenesis and tumor progression. ICAM-1 modulates the susceptibility to several types of cancer and the disease prognosis; however, its role in epithelial ovarian cancer (EOC) is unclear. Here, we evaluate single nucleotide polymorphisms (SNPs) in ICAM-1 as predictors of EOC risk and prognosis. Six ICAM-1 polymorphisms were genotyped in 408 patients with EOC and 520 controls using the MassARRAY system. The ICAM-1 mRNA levels in 89 EOC tissues and 35 normal ovarian tissues were examined using quantitative PCR. The ICAM-1 rs5498 G allele was associated with increased tumor grade (OR = 2.650) and EOC risk (OR = 1.405). This risk was more evident in females who had first-degree relatives (FDRs) with a tumor (OR = 3.475) or who experienced early menarche (OR = 2.774). The ICAM-1 expression in the cancerous tissue was elevated compared with that of normal ovarian tissues (p < 0.0001), and it was associated with an rs5498 genotype (p = 0.0002). ICAM-1 SNPs did not significantly predict the overall EOC survival (p > 0.05). However, the rs5498 G allele correlated with EOC survival time in patients whose FDRs suffered from a tumor (p = 0.001). ICAM-1 rs5498 likely confers a high risk for EOC in G allele carriers accompanied by up-regulation of ICAM-1 expression during carcinogenesis. The combination of ICAM-1 rs5498 and tumor history predicts the EOC prognosis.     

Identifying disease related sub-pathways for analysis of genome-wide association studies

Most methods for genome-wide association studies (GWAS) focus on discovering a single genetic variant, but the pathogenesis of complex diseases is thought to arise from the joint effect of multiple genetic variants. Information about pathway structure, such as the interactions and distances between gene products within pathways, can help us learn more about the functions and joint effect of genes associated with disease risk. We developed a novel sub-pathway based approach to study the joint effect of multiple genetic variants that are modestly associated with disease. The approach prioritized sub-pathways based on the significance values of single nucleotide polymorphisms (SNPs) and the interactions and distances between gene products within pathways. We applied the method to seven complex diseases. The result showed that our method can efficiently identify statistically significant sub-pathways associated with the pathogenesis of complex diseases. The approach identified sub-pathways that may inform the interpretation of GWAS data.     

Evaluating the Predictive Value of Biomarkers with Stratified Case‐Cohort Design

Summary Identification of novel biomarkers for risk assessment is important for both effective disease prevention and optimal treatment recommendation. Discovery relies on the precious yet limited resource of stored biological samples from large prospective cohort studies. Case‐cohort sampling design provides a cost‐effective tool in the context of biomarker evaluation, especially when the clinical condition of interest is rare. Existing statistical methods focus on making efficient inference on relative hazard parameters from the Cox regression model. Drawing on recent theoretical development on the weighted likelihood for semiparametric models under two‐phase studies ( Breslow and Wellner, 2007 ), we propose statistical methods to evaluate accuracy and predictiveness of a risk prediction biomarker, with censored time‐to‐event outcome under stratified case‐cohort sampling. We consider nonparametric methods and a semiparametric method. We derive large sample properties of proposed estimators and evaluate their finite sample performance using numerical studies. We illustrate new procedures using data from Framingham Offspring Study to evaluate the accuracy of a recently developed risk score incorporating biomarker information for predicting cardiovascular disease.     

Pediatricians’ Own Weight: Self‐perception,Misclassification, and Ease of Counseling

Objectives: Pediatricians underdiagnose overweight and feel ineffective at counseling. Given the relationship between physicians’ health and health habits and counseling behaviors, we sought to determine the 1) percentage of pediatricians who are overweight; 2) accuracy of pediatricians’ own weight status classification; and 3) relationship between weight self‐perception and perceived ease of obesity counseling. Research Methods and Procedures: This study was a cross‐sectional, mail survey of North Carolina pediatricians that queried about their weight status and ease of counseling. Accuracy of pediatricians’ self‐classification of weight status was compared with BMIs derived from self‐reported height and weight. Using logistic regression, controlling for potential confounding variables, we examined the association between weight perception and ease of counseling. Results: The unadjusted response rate was 62%, and the adjusted response rate was 71% (n = 355). Nearly one‐half (49%) of overweight pediatricians did not identify themselves as such. Men had greater adjusted odds of misclassifying overweight than women [odds ratio (OR), 3.61; 95% confidence interval (CI) = 1.81, 7.21]. Self‐classified “thin” pediatricians had nearly six times the odds of reporting more counseling difficulty as a result of their weight than “average” weight pediatricians (OR = 5.69; 95% CI = 2.30, 14.1), and self‐identified “overweight” pediatricians reported nearly four times as great counseling difficulty as “average” weight physicians (OR = 3.84; 95% CI = 1.11, 13.3), after adjustment for self‐reported BMI weight status and other potential confounders. Discussion: The roles that physician weight misclassification and self‐perception potentially play in influencing rates of obesity counseling warrant further research.     

MDR1基因单靶点双荧光素酶报告基因系统的建立

目的通过构建以MDR1启动子为启动序列的双荧光素酶报告基因系统并进行活性分析,为MDR1基因表达的单靶点调控研究和逆转剂的筛选提供一种有效的方法。方法从HCT-8细胞中提取DNA并克隆含有MDR1基因启动子中Y—box序列。将该序列重组到萤光素酶报告基因载体pGL-3．Basic的启动区域中,从而构建报告基因载体pGL-MDR1。将pGL-MDR1和pRL-TK载体共转染到HCT-8和HCT-8／VCR细胞中。通过调节不同载体的比例来优化转染效率。利用MDRI基因激活剂（热诱导）和抑制剂（EGCG）等处理来分析其启动转录活性受外界因素的影响。结果通过直接测序法验证了pGL-MDR1含有MDR1基因启动子Y—box序列且没有出现碱基突变。在pGL-MDR1和pRL-TK的转染比例为5：5时,转染效率最高并具有最高的萤光素酶活性。通过MDR1基因激活处理后表现为时间依赖性地激活MDR1基因的表达,而MDR1基因抑制剂的作用则相反。结论MDR1启动子为启动序列的双荧光素酶报告基因系统建立成功。该系统不但可以用于研究活体生物发光成像和MDRI基因表达的机理,而且可用于单靶点的多药耐药抑制剂的筛选。     

Biostatistical aspects of genome-wide association studies

To search the entire human genome for association is a novel and promising approach to unravelling the genetic basis of complex genetic diseases. In these genome-wide association studies (GWAs), several hundreds of thousands of single nucleotide polymorphisms (SNPs) are analyzed at the same time, posing substantial biostatistical and computational challenges. In this paper, we discuss a number of biostatistical aspects of GWAs in detail. We specifically consider quality control issues and show that signal intensity plots are a sine qua condition non in today's GWAs. Approaches to detect and adjust for population stratification are briefly examined. We discuss different strategies aimed at tackling the problem of multiple testing, including adjustment of p -values, the false positive report probability and the false discovery rate. Another aspect of GWAs requiring special attention is the search for gene-gene and gene-environment interactions. We finally describe multistage approaches to GWAs.     

Life cycle assessment of commercial furniture: a case study of Formway LIFE chair

Background, aims and scope  The environmental aspects of companies and their products are becoming more significant in delivering competitive advantage. Formway Furniture, a designer and manufacturer of office furniture products, is a New Zealand-based company that is committed to sustainable development. It manufactures two models of the light, intuitive, flexible and environmental (LIFE) office chair: one with an aluminium base and one with a glass-filled nylon (GFN) base. It was decided to undertake a life cycle assessment (LCA) study of these two models in order to: (1) determine environmental hotspots in the life cycle of the two chairs (goal 1); (2) compare the life cycle impacts of the two chairs (goal 2); and (3) compare alternative potential waste-management scenarios (goal 3). The study also included sensitivity analysis with respect to recycled content of aluminium in the product. Materials and methods  The LIFE chair models consist of a mix of metal and plastic components manufactured by selected Formway suppliers according to design criteria. Hence, the research methodology included determining the specific material composition of the two chair models and acquisition of manufacturing data from individual suppliers. These data were compiled and used in conjunction with pre-existing data, specifically from the ecoinvent database purchased in conjunction with the SimaPro7 LCA software, to develop the life cycle inventory of the two chair models. The life cycle stages included in the study extended from raw-material extraction through to waste management. Impact assessment was carried out using CML 2 baseline 2000, the methodology developed by Leiden University’s Institute for Environmental Sciences. Results  This paper presents results for global warming potential (GWP100). The study showed a significant impact contribution from the raw-material extraction/refinement stage for both chair models; aluminium extraction and refining made the greatest contribution to GWP100. The comparison of the two LIFE chair models showed that the model with the aluminium base had a higher GWP100 impact than the model with the GFN base. The waste-management scenario compared the GWP100 result when (1) both chair models were sent to landfill and (2) steel and aluminium components were recycled with the remainder of the chair sent to landfill. The results showed that the recycling scenario contributed to a reduced GWP100 result. Since production and processing of aluminium was found to be significant, a sensitivity analysis was carried out to determine the impact of using aluminium with different recycled contents (0%, 34% and 100%) in both waste-management scenarios; this showed that increased use of recycled aluminium was beneficial. The recycling at end-of-life scenarios was modelled using two different end-of-life allocation approaches, i.e. consequential and attributional, in order to illustrate the variation in results caused by choice of allocation approach. The results using the consequential approach showed that recycling at end-of-life was beneficial, while use of the attributional method led to a similar GWP100 as that seen for the landfill scenario. Discussion  The results show that the main hotspot in the life cycle is the raw-material extraction/refinement stage. This can be attributed to the extraction and processing of aluminium, a material that is energy intensive. The LIFE chair model with the aluminium base has a higher GWP100 as it contains more aluminium. Sensitivity analysis pertaining to the recycled content of aluminium showed that use of aluminium with high recycled content was beneficial; this is because production of recycled aluminium is less energy intensive than production of primary aluminium. The waste-management scenario showed that recycling at end-of-life resulted in a significantly lower GWP100 than landfilling at end-of-life. However, this result is dependent upon the modelling approach used for recycling. Conclusions  With respect to goal 1, the study found that the raw-material extraction/refinement stage of the life cycle was a significant factor for both LIFE chair models. This was largely due to the use of aluminium in the product. For goal 2, it was found that the LIFE chair model with the aluminium base had a higher GWP100 than the GFN model, again due to the material content of the two models. Results for goal 3 illustrated that recycling at end-of-life is beneficial when using a system expansion (consequential) approach to model recycling; if an attributional ‘cut-off’ approach is used to model recycling at end-of-life, there is virtually no difference in the results between landfilling and recycling. Sensitivity analysis pertaining to the recycled content of aluminium showed that use of higher recycled contents leads to a lower GWP100 impact. Recommendation and perspectives  Most of the GWP100 impact was contributed during the raw-material extraction/refinement stage of the life cycle; thus, the overall impact of both LIFE chair models may be reduced through engaging in material choice and supply chain environmental management with respect to environmental requirements. The study identified aluminium components as a major contributor to GWP100 for both LIFE chair models and also highlighted the sensitivity of the results to its recycled content. Thus, it is recommended that the use of aluminium in future product designs be limited unless it is possible to use aluminium with a high recycled content. With respect to waste management, it was found that a substantial reduction in the GWP100 impact would occur if the chairs are recycled rather than landfilled, assuming an expanding market for aluminium. Thus, recycling the two LIFE chair models at end-of-life is highly recommended.     

Case Fatality Proportion

A precise definition of case fatality proportion for compartmental disease transmission models with disease induced mortality rate is given. This is applied in classical epidemic modeling frameworks to models with multiple infectious stages, with multi-groups, with spatial patches, and with age of infection. It is shown that the case fatality proportion is the sum over all stages of the product of the probability of dying from the disease at a given stage and the probability of surviving to that stage. The derived expressions for case fatality can be used to estimate the disease induced death rates from more readily available data.