BACKGROUND & AIMS: :Construction of tissue microarrays (TMAs) to efficiently characterize large sets of noninvasive epithelial lesions in the breast by immunohistochemistry is an appealing investigative approach, but presents technical challenges. We report methodologic studies performed to optimize methods for building TMAs from noninvasive breast tissues collected in a large case-control study of breast cancer. Using a manual arraying technique with 2.0-mm diameter needles, we constructed TMAs from specimens obtained from 32 women with breast cancer containing the following targets: (1) 28 terminal duct lobular units (TDLUs); (2) 28 ductal carcinomas in situ, and (3) 23 invasive carcinomas. Using careful target selection, we achieved representation of approximately 80% of noninvasive targets with sustained preservation through section 30 of the TMAs. Immunohistochemical staining of TDLU targets demonstrated positive staining for estrogen receptor (ER) in 30.8% of tubules and for progesterone receptor (PR) in 50.0%. To establish an efficient method to evaluate staining results in TDLUs, we created a categorical scoring system to approximate the percentage of tubules containing positive stained cells (<10%, 10% to 50%, >or=50%), and compared the results with those obtained by tubule counting. Comparison between the two methods demonstrated exact agreement for 70.8% of ER and 79.2% of PR stains without two-category discrepancies. ER/PR expression levels in multiple (up to 4) noninvasive targets of the same tissue type (TDLU or DCIS) from a single block showed good correlation. These data suggest that it is feasible to produce TMAs of noninvasive breast structures, albeit with careful selection of targets, and that immunostains of such cores may permit efficient immunohistochemical characterization of peritumoral tissues. Additional exploration of this approach is needed.

背景与目标： : 通过免疫组织化学构建组织微阵列 (tma) 以有效表征乳房中大量非侵入性上皮病变是一种吸引人的研究方法，但存在技术挑战。我们报告了方法学研究，以优化从大型乳腺癌病例对照研究中收集的非侵入性乳腺组织中构建TMAs的方法。使用具有2.0毫米直径针头的手动排列技术，我们从32名乳腺癌妇女获得的标本中构建了TMAs，这些标本包含以下目标 :( 1) 28个末端导管小叶单位 (TDLUs); (2) 28个原位导管癌和 (3) 23个浸润性癌。通过仔细的靶标选择，我们通过TMAs的第30节获得了约80% 的非侵入性靶标的持续保存。TDLU靶标的免疫组织化学染色显示肾小管30.8% 中的雌激素受体 (ER) 和50.0% 中的孕激素受体 (PR) 呈阳性染色。为了建立一种有效的方法来评估TDLUs中的染色结果，我们创建了一个分类评分系统来近似包含阳性染色细胞 (<10%，10% 至50%，> 或 = 50%) 的小管的百分比，并将结果与通过小管计数获得的结果进行比较。两种方法之间的比较表明，ER的70.8% 和PR染色的79.2% 完全一致，没有两类差异。来自单个块的相同组织类型 (TDLU或DCIS) 的多个 (最多4个) 非侵入性靶标中的ER/PR表达水平显示出良好的相关性。这些数据表明，尽管仔细选择了靶标，但产生非侵入性乳房结构的tma是可行的，并且此类核心的免疫染色可能允许对瘤周组织进行有效的免疫组织化学表征。需要对这种方法进行进一步的探索。

BACKGROUND & AIMS: :In this paper we describe a biological indicator which can be used to study the behavior of Vibrio vulnificus, an important molluscan shellfish-associated human pathogen. A V. vulnificus ATCC 27562 derivative that expresses green fluorescent protein (GFP) and kanamycin resistance was constructed using conjugation. Strain validation was performed by comparing the GFP-expressing strain (Vv-GFP) and the wild-type strain (Vv-WT) with respect to growth characteristics, heat tolerance (45 degrees C), freeze-thaw tolerance (-20(o) and -80 degrees C), acid tolerance (pH 5.0, 4.0, and 3.5), cold storage tolerance (5 degrees C), cold adaptation (15 degrees C), and response to starvation. Levels of recovery were evaluated using nonselective medium (tryptic soy agar containing 2% NaCl) with and without sodium pyruvate. The indicator strain was subsequently used to evaluate the survival of V. vulnificus in oysters exposed to organic acids (citric and acetic acids) and various cooling regimens. In most cases, Vv-GFP was comparable to Vv-WT with respect to growth and survival upon exposure to various biological stressors; when differences between the GFP-expressing and parent strains occurred, they usually disappeared when sodium pyruvate was added to media. When V. vulnificus was inoculated into shellstock oysters, the counts dropped 2 log(10) after 11 to 12 days of refrigerated storage, regardless of the way in which the oysters were initially cooled. Steeper population declines after 12 days of refrigerated storage were observed for both iced and refrigerated products than for slowly cooled product and product held under conservative harvest conditions. By the end of the refrigeration storage study (22 days), the counts of Vv-GFP in iced and refrigerated oysters had reached the limit of detection (10(2) CFU/oyster), but slowly cooled oysters and oysters stored under conservative harvest conditions still contained approximately 10(3) and >10(4) CFU V. vulnificus/oyster by day 22, respectively. The Vv-GFP levels in the oyster meat remained stable for up to 24 h when the meat was exposed to acidic conditions at various pH values. Ease of detection and comparability to the wild-type parent make Vv-GFP a good candidate for use in studying the behavior of V. vulnificus upon exposure to sublethal stressors that might be encountered during postharvest handling of molluscan shellfish.

背景与目标： : 在本文中，我们描述了一种生物学指标，可用于研究创伤弧菌 (一种与软体动物贝类相关的重要人类病原体) 的行为。使用缀合物构建表达绿色荧光蛋白 (GFP) 和卡那霉素抗性的创伤弧菌ATCC 27562衍生物。通过比较表达GFP的菌株 (vv-gfp) 和野生型菌株 (vv-wt) 在生长特性，耐热性 (45 ℃)，冻融耐受性 (-20(o) 和-80 ℃) 方面进行菌株验证，耐酸性 (pH 5.0、4.0和3.5) 、耐冷性 (5 ℃) 、冷适应 (15 ℃) 和对饥饿的响应。使用含和不含丙酮酸钠的非选择性培养基 (含2% NaCl的胰蛋白酶大豆琼脂) 评估回收率水平。随后使用指示菌株评估暴露于有机酸 (柠檬酸和乙酸) 和各种冷却方案的牡蛎中vulnificus的存活率。在大多数情况下，Vv-GFP在暴露于各种生物应激源后的生长和存活方面与Vv-WT相当; 当表达GFP的菌株和亲本菌株之间发生差异时，当向培养基中添加丙酮酸钠时，它们通常消失。当将vulnificus接种到贝壳类牡蛎中时，冷藏储存11至12天后，计数下降了2 log(10)，而与最初冷却牡蛎的方式无关。冷藏和冷藏产品在冷藏12天后的种群数量下降幅度均大于缓慢冷却的产品和在保守收获条件下保存的产品。到冷藏储存研究结束时 (22天)，冰镇牡蛎和冷藏牡蛎中Vv-GFP的计数已达到检测极限 (10(2) CFU/牡蛎)，但是缓慢冷却的牡蛎和在保守收获条件下储存的牡蛎到第22天仍然分别含有大约10(3) 和> 10(4) CFU V. vulnificus/牡蛎。当将肉暴露于各种ph值的酸性条件下时，牡蛎肉中的Vv-GFP水平保持稳定长达24小时。易于检测和与野生型亲本的可比性使vv-gfp成为研究暴露于软体动物贝类收获后可能遇到的亚致死性应激源时的创伤弧菌行为的良好候选者。

BACKGROUND & AIMS: INTRODUCTION:Impulsivity is a symptom of several disorders such as personality disorder, bipolar disorder, suicidal behaviour, substance use disorders, schizophrenia...Forensic psychiatry is particularly concerned with impulsivity. It increases the risk of violence among clinical populations and figures in various instruments such as the HCR-20, the VRAG and the PCL-R to assess violence risk. It is one of many dimensions that can lead to aggressive behaviour among psychiatric patients. The Barratt Impulsiveness Scale (BIS), in its 11th version, is a 30-item self-report instrument that helps assessing impulsivity trait among normal and clinical populations. The BIS is the most commonly administered self-assessment of impulsiveness. As of March 2009, there have been 551 citations of the BIS-11 among many publications. The purpose of the present study is to examine the psychometric properties of the Arabic translation of the BIS-11th version in a sample of the general population and to identify an eventual correlation between impulsivity and socio-demographic characteristics. PATIENTS AND METHODS:This is a prospective study conducted over a five-month period, from June to October 2010, and including 134 persons from the general population having provided their informed consent. The dialectal Arabic version was carried out by translation from English to dialectal Arabic followed by a back translation to English. Some questions were modified to be understood by a population with low education. After giving their verbal informed consent, the participants filled in the Arabic version of the BIS-11. For the illiterate, responses and quotations were performed by the interviewer. The persons were also asked to fill in socio-demographic data. Cronbach's coefficient was calculated, and then we assessed impulsivity prevalence and a correlation between demographic features and impulsivity scores. For the analyses, the statistical software SPSS 11 was used. RESULTS:The sex ratio is 1.02. Most of the interviewed persons were 20 to 49 years old. Around 25.4% of the sample were analphabets, 32.1% had primary education, 29.1% had secondary education and 13.4% were undergraduates. The Cronbach's alpha was respectively 0.66 for attention, 0.72 for motor impulsivity, 0.61 for lack of planning and 0.78 for total impulsivity. Factor analysis identified three factors explaining the total variance of 32.6%. Impulsivity prevalence was 9%. We did not find significant correlation between demographic features and impulsivity scores. DISCUSSION:Limits of the study: scale stability over time was not verified. This was due to the difficulty in re-inviting the same persons to fulfil the scale a second time. Because no instrument for assessing exists in Arabic, comparison was not possible between the translated Barratt's scale and the reference. Our sample represents the general population. This choice was justified in order to study an eventual correlation between impulsiveness and socio-demographic characteristics. We must mention difficulties when asking persons with low education to complete the scale, what may have caused a poorer performance of the scale due to difficulties in understanding some questions. Moreover, we had chosen a non-clinical sample. The validation of the scale could be performed in a clinical population. The measure of internal consistency (Cronbach's alpha) fell within an acceptable range (0.61-0.78), suggesting that the Arabic version of the BIS-11 is reliable. Exploratory factor analysis of the current version identified three factors, but these factors differed from those of other translated versions. CONCLUSION:There is growing interest in the impulsivity concept. Forensic psychiatry is particularly concerned by impulsivity. In fact, it is related to psychiatric patients' violence. Impulsivity also reveals the problem of responsibility assessment in psychiatric expertise and the dangerousness of psychiatric patients. The Arabic version of the BIS-11 has a good apparent and internal consistency. This version could be useful in assessing psychiatric patient's dangerousness.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Predicted maturity offset and age at peak height velocity are increasingly used with youth athletes, although validation studies of the equations indicated major limitations. The equations have since been modified and simplified. OBJECTIVE:The objective of this study was to validate the new maturity offset prediction equations in independent longitudinal samples of boys and girls. METHODS:Two new equations for boys with chronological age and sitting height and chronological age and stature as predictors, and one equation for girls with chronological age and stature as predictors were evaluated in serial data from the Wrocław Growth Study, 193 boys (aged 8-18 years) and 198 girls (aged 8-16 years). Observed age at peak height velocity for each youth was estimated with the Preece-Baines Model 1. The original prediction equations were included for comparison. Predicted age at peak height velocity was the difference between chronological age at prediction and maturity offset. RESULTS:Predicted ages at peak height velocity with the new equations approximated observed ages at peak height velocity in average maturing boys near the time of peak height velocity; a corresponding window for average maturing girls was not apparent. Compared with observed age at peak height velocity, predicted ages at peak height velocity with the new and original equations were consistently later in early maturing youth and earlier in late maturing youth of both sexes. Predicted ages at peak height velocity with the new equations had reduced variation compared with the original equations and especially observed ages at peak height velocity. Intra-individual variation in predicted ages at peak height velocity with all equations was considerable. CONCLUSION:The new equations are useful for average maturing boys close to the time of peak height velocity; there does not appear to be a clear window for average maturing girls. The new and original equations have major limitations with early and late maturing boys and girls.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Recurrent aphthous stomatitis (RAS) is characterized by painful recurrent oral ulcers and is typically diagnosed via history and clinical examination. Our aim was to validate a set of anamnestic diagnostic criteria (RASDX) to increase the accuracy of RAS diagnosis, particularly when a clinical examination is not feasible. METHODS:Participants were enrolled during an unmatched case-control study. RASDX consisted of an initial phone screening using standardized questionnaires and recognition of RAS photographs in the clinic. The proportion of agreement with an examination by an oral medicine expert was calculated. RESULTS:A total of 115 participants were scheduled for a clinical diagnostic visit and 11 were withdrawn. The remaining 104 participants were aged 18-50 years, 54% women, 64% White and 20% Hispanic. Of these, all 49 controls with negative RASDX had no clinical ulcers. Of the 54 cases diagnosed with RAS by RASDX, 53 were clinically confirmed to have RAS lesions (99% agreement; exact one-sided 95% CI = 95-100%). CONCLUSIONS:RASDX, based on a combination of history and photograph recognition, was highly accurate compared with a diagnosis that employed an oral examination.

背景与目标：

BACKGROUND & AIMS: :Understanding the impact of peripheral artery disease (PAD) requires broad evaluation of how functional limitations of PAD affect patients' perceptions of health-related quality of life (HRQL). The objective of this study was to describe the development, testing, and psychometric properties of the PAD Quality of Life Questionnaire (PADQOL). The PADQOL was developed in three steps: (1) interviews of symptomatic PAD patients provided content of the initial questionnaire; (2) co-administration with the SF-36 (a 36-item short-form health survey), Walking Impairment Questionnaire, and Profile of Mood States examined construct validity; and (3) a three-phased factor analysis identified factors and shortened the questionnaire. Data analyses from 297 symptomatic PAD patients resulted in a 38-item questionnaire of five factors: Social relationships and interactions, Self-concept and feelings, Symptoms and limitations in physical functioning, Fear and uncertainty, and Positive adaptation (α = 0.92-0.73) and items related to sexual function, intimate relationships and employment. Between-instrument correlations established construct validity. In conclusion, PADQOL is a validated measure to assess the disease-specific physical, psychosocial and emotional effects of PAD for research and practice.

背景与目标： : 了解外周动脉疾病 (PAD) 的影响需要广泛评估PAD的功能局限性如何影响患者对健康相关生活质量 (HRQL) 的看法。这项研究的目的是描述PAD生活质量问卷 (PADQOL) 的开发，测试和心理测量特性。PADQOL分为三个步骤 :( 1) 对有症状的PAD患者的访谈提供了初始问卷的内容; (2) 与SF-36共同给药 (一项36项简短的健康调查)，步行障碍问卷和情绪状态的概况检查结构效度; (3) 三个阶段的因素分析确定了因素并缩短了问卷。297名有症状的PAD患者的数据分析得出了一个38项问卷，其中包括五个因素: 社会关系和互动，自我概念和感觉，身体功能的症状和局限性，恐惧和不确定性以及积极适应 (α = 0.92-0.73) 和与性功能相关的项目，亲密关系和就业。工具间相关性建立了结构效度。总之，PADQOL是一种经过验证的措施，可评估PAD对特定疾病的身体，社会心理和情感影响，以进行研究和实践。

BACKGROUND & AIMS: INTRODUCTION:This project addresses the validation study design of a test system using a telemetered non-human primate model for cardiovascular safety pharmacology evaluation. METHODS:The validation provided by the supplier evaluated installation (IQ) and operation (OQ) qualifications. This protocol was completed with tests evaluating electronic data management and accuracy and precision of transmitter (n=4) measurements for temperature and pressure criteria with a series of tested values. As part of performance qualification, physical activity (for 24 h) as well as cardiovascular, ECG (20 complexes for each animal) and systemic arterial blood pressure (SAP, 10 different measures), data were recorded simultaneously from the same animals (n=4) using certified equipment and the telemetry system. Reliability was evaluated over 60 days. RESULTS:The IQ and OQ were completed successfully. The electronic data management was performed successfully. The ex-vivo evaluation for temperature and pressure showed high correlation (R(2)>0.99) but with a slight pressure shift, as expected, with this transmitter model. For physical activity, the correlation coefficients were good to excellent with high activity counts but the comparison demonstrated a limited sensitivity of the telemetry system with animal presenting low activity levels. ECG interval measurement using the telemetry software was considered at least equivalent to manual measurement, but with some limitations in the reading of the ECG. The comparison between both methods of SAP measurement showed adequate precision (R(2)=0.969) but no accuracy. DISCUSSION:Reference monitoring methods are important to ensure proper test system validation. Monitoring with a reference methodology and the telemetry system is important in order to evaluate precision and accuracy of the test system. Computerized analysis may lack the capability to analyze ECG complexes with abnormal morphologies. This reinforces the need to have ECG evaluation prior to telemetry implantation along with visual evaluation of ECG tracing at standard speed (e.g. 50 mm/s) at all time points.

背景与目标：

BACKGROUND & AIMS: :sigma(28) RNA polymerase is an alternative RNA polymerase that has been proposed to have a role in late developmental gene regulation in Chlamydia, but only a single target gene has been identified. To discover additional sigma(28)-dependent genes in the Chlamydia trachomatis genome, we applied bioinformatic methods using a probability weight matrix based on known sigma(28) promoters in other bacteria and a second matrix based on a functional analysis of the sigma(28) promoter. We tested 16 candidate sigma(28) promoters predicted with these algorithms and found that 5 were active in a chlamydial sigma(28) in vitro transcription assay. hctB, the known sigma(28)-regulated gene, is only expressed late in the chlamydial developmental cycle only, and two of the newly identified sigma(28) target genes (tsp and tlyC_1) also have late expression profiles, providing support for sigma(28) as a regulator of late gene expression. One of the other novel sigma(28)-regulated genes is dnaK, a known heat shock-responsive gene, suggesting that sigma(28) RNA polymerase may be involved in the response to cellular stress. Our sigma(28) prediction algorithm can be applied to other bacteria, and by performing a similar analysis on the Escherichia coli genome, we have predicted and functionally identified five previously unknown sigma(28)-regulated genes in E. coli.

背景与目标： : sigma(28) RNA聚合酶是一种替代的RNA聚合酶，已被提议在衣原体的晚期发育基因调控中起作用，但仅鉴定出单个靶基因。为了在沙眼衣原体基因组中发现其他依赖sigma(28) 的基因，我们使用生物信息学方法，使用基于其他细菌中已知sigma(28) 启动子的概率权重矩阵和基于sigma(28) 启动子的功能分析的第二个矩阵。28) 启动子。我们测试了用这些算法预测的16个候选sigma(28) 启动子，发现5个在衣原体sigma(28) 体外转录测定中具有活性。已知的sigma(28) 调控基因hctB仅在衣原体发育周期的晚期表达，新鉴定的sigma(28) 靶基因 (tsp和tlyC_1) 中的两个也具有晚期表达谱，为sigma(28) 作为晚期基因表达的调节剂提供支持。另一个新的sigma(28) 调控基因是dnaK，这是一种已知的热休克反应基因，表明sigma(28) RNA聚合酶可能参与了对细胞应激的反应。我们的sigma(28) 预测算法可以应用于其他细菌，并且通过对大肠杆菌基因组进行类似的分析，我们已经预测并在功能上鉴定了大肠杆菌中五个以前未知的sigma(28) 调控基因。

BACKGROUND & AIMS: BACKGROUND:Accurate measurement of physical activity patterns can be used to identify sedentary behaviour and may facilitate interventions aimed at reducing inactivity. OBJECTIVE:To evaluate the activPAL physical activity monitor as a measure of posture and motion in everyday activities using observational analysis as the criterion standard. METHODS:Wearing three activPAL monitors, 10 healthy participants performed a range of randomly assigned everyday tasks incorporating walking, standing and sitting. Each trial was captured on a digital camera and the recordings were synchronised with the activPAL. The time spent in different postures was visually classified and this was compared with the activPAL output. RESULTS:Intraclass correlation coefficients (ICC 2,1) for interdevice reliability ranged from 0.79 to 0.99. Using the Bland and Altman method, the mean percentage difference between the activPAL monitor and observation for total time spent sitting was 0.19% (limits of agreement -0.68% to 1.06%) and for total time spent upright was -0.27% (limits of agreement -1.38% to 0.84%). The mean difference for total time spent standing was 1.4% (limits of agreement -6.2% to 9.1%) and for total time spent walking was -2.0% (limits of agreement -16.1% to 12.1%). A second-by-second analysis between observer and monitor found an overall agreement of 95.9%. CONCLUSION:The activPAL activity monitor is a valid and reliable measure of posture and motion during everyday physical activities.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:To validate the SAPS 3 admission prognostic model in patients with cancer admitted to the intensive care unit (ICU). DESIGN:Cohort study. SETTING:Ten-bed medical-surgical oncologic ICU. PATIENTS AND PARTICIPANTS:Nine hundred and fifty-two consecutive patients admitted over a 3-year period. INTERVENTIONS:None. MEASUREMENTS AND RESULTS:Data were prospectively collected at admission of ICU. SAPS II and SAPS 3 scores with respective estimated mortality rates were calculated. Discrimination was assessed by area under receiver operating characteristic (AUROC) curves and calibration by Hosmer-Lemeshow goodness-of-fit test. The mean age was 58.3+/-23.1 years; there were 471 (49%) scheduled surgical, 348 (37%) medical and 133 (14%) emergency surgical patients. ICU and hospital mortality rates were 24.6% and 33.5%, respectively. The mean SAPS 3 and SAPS II scores were 52.3+/-18.5 points and 35.3+/-20.7 points, respectively. All prognostic models showed excellent discrimination (AUROC>or=0.8). The calibration of SAPS II was poor (p<0.001). However, the calibration of standard SAPS 3 and its customized equation for Central and South American (CSA) countries were appropriate (p>0.05). SAPS II and standard SAPS 3 prognostic models tended somewhat to underestimate the observed mortality (SMR>1). However, when the customized equation was used, the estimated mortality was closer to the observed mortality [SMR=0.95 (95% CI=0.84-1.07)]. Similar results were observed when scheduled surgical patients were excluded. CONCLUSIONS:The SAPS 3 admission prognostic model at ICU admission, in particular its customized equation for CSA, was accurate in our cohort of critically ill patients with cancer.

背景与目标：

BACKGROUND & AIMS: :Water plays an active role in many fundamental phenomena in cellular systems such as molecular recognition, folding and conformational equilibria, reaction kinetics and phase partitioning. Hence, our ability to account for the energetics of these processes is highly dependent on the models we use for calculating solvation effects. For example, theoretical prediction of protein-ligand binding modes (i.e., docking) and binding affinities (i.e., scoring) requires an accurate description of the change in hydration that accompanies solute binding. In this review, we discuss the challenges of constructing solvation models that capture these effects, with an emphasis on continuum models and on more recent developments in the field. In our discussion of methods, relatively greater attention will be given to boundary element solutions to the Poisson equation and to nonpolar solvation models, two areas that have become increasingly important but are likely to be less familiar to many readers. The other focus will be upon the trending efforts for evaluating solvation models in order to uncover limitations, biases, and potentially attractive directions for their improvement and applicability. The prospective and retrospective performance of a variety of solvation models in the SAMPL blind challenges will be discussed in detail. After just a few years, these benchmarking exercises have already had a tangible effect in guiding the improvement of solvation models.

背景与目标： : 水在细胞系统中的许多基本现象中起着积极作用，例如分子识别，折叠和构象平衡，反应动力学和相分配。因此，我们解释这些过程的能量学的能力在很大程度上取决于我们用于计算溶剂化效应的模型。例如，蛋白质-配体结合模式 (即对接) 和结合亲和力 (即评分) 的理论预测需要准确描述伴随溶质结合的水合变化。在这篇综述中，我们讨论了构建捕获这些影响的溶剂化模型的挑战，重点是连续模型和该领域的最新发展。在我们对方法的讨论中，将相对更多地关注泊松方程的边界元解和非极性溶剂化模型，这两个领域已变得越来越重要，但许多读者可能不太熟悉。另一个重点将放在评估溶剂化模型的趋势上，以发现局限性，偏见以及其改进和适用性的潜在吸引力方向。将详细讨论SAMPL盲挑战中各种溶剂化模型的前瞻性和回顾性表现。短短几年后，这些基准测试工作已经在指导溶剂化模型的改进方面产生了切实的效果。

BACKGROUND & AIMS: BACKGROUND:Oral health literacy is a newly emerging field with considerable research potential. AIM:To validate an original instrument, the Hong Kong Oral Health Literacy Assessment Task (HKOHLAT-P) for paediatric dentistry. DESIGN:A convenient sample of 200 child/parent dyads attending a dental hospital in Hong Kong was selected. Convergent validity was tested by examining the association of HKOHLAT-P scores with those derived from the Test of Functional Health Literacy in Dentistry (TOFHLiD) and Hong Kong Rapid Estimate of Adult Literacy in Dentistry (HKREALD-30). The predictive validity of HKOHLAT-P was determined by testing the association between HKOHLAT-P and children's caries experience (dmft) and the Chinese Early Childhood Oral Health Impact Scale (ECOHIS). The test-retest reliability and internal consistency of HKOHLAT-P were also evaluated. RESULTS:HKOHLAT-P was positively correlated with TOFHLiD and HKREALD-30 (P < 0.01), and was negatively correlated with children's dmft and ECOHIS. In the regression model, HKOHLAT-P was associated with TOFHLiD, HKEALD-30, children's dmft, and ECOHIS (P < 0.05) after controlling for participants' demographic characteristics. The intra-class correlation coefficient of HKOHLAT-P was 0.63 and the Cronbach's α was 0.71. CONCLUSION:Initial testing of HKOHLAT-P suggested that it is a valid and reliable instrument.

背景与目标：

BACKGROUND & AIMS: AIMS:To reduce sudden cardiac death, implantable cardioverter-defibrillators (ICDs) are indicated in patients with ischaemic and non-ischaemic dilated cardiomyopathy and a left ventricular ejection fraction (LVEF) ≤35%. Current guidelines do not recommend device therapy in patients with a life expectancy <1 year since benefit in these patients is low. In this study, we evaluated the incidence and predictors of early mortality (<1 year after implantation) in a consecutive primary prevention population. METHODS AND RESULTS:Analysis was performed on a prediction and validation cohort. The primary endpoint was all-cause mortality at 1 year. The prediction cohort comprised 861 prophylactic ICD recipients with ischaemic cardiomyopathy or dilated cardiomyopathy from the Academic Medical Center (Amsterdam) and Thorax Center Twente (Enschede). Detailed clinical data were collected. After multivariate analysis, a risk score was developed based on age ≥75 years, LVEF ≤ 20%, history of atrial fibrillation, and estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m(2). Using these predictors, a low (≤1 factor), intermediate (2 factors), and high (≥3 factors) risk group could be identified with 1-year mortality of, respectively, 3.4, 10.9, and 38.9% (P< 0.01). Afterwards, the risk score was validated in 706 primary prevention patients from the Erasmus Medical Center (Rotterdam). One-year mortality was, respectively, 2.5, 13.2, and 46.3% (all P< 0.01). CONCLUSION:A simple risk score based on age, LVEF, eGFR, and atrial fibrillation can identify patients at low, intermediate, and high risk for early mortality after ICD implantation. This may be helpful in the risk assessment of ICD candidates.

背景与目标：

BACKGROUND & AIMS: :Successful translation of findings derived from preclinical studies into effective therapies is critical in biomedical research. Lack of robustness and reproducibility of the preclinical data, due to insufficient number of repeats, inadequate cell-based and mouse models contribute to the poor success rate. Antibodies are widely used in preclinical research, notably to determine the expression of potential therapeutic targets in tissues of interest, including tumors, but also to identify disease and/or treatment response biomarkers. We sought to determine whether the current antibody characterization standards in preclinical research are sufficient to ensure reliability of the data found in peer-reviewed publications. To address this issue, we used detection of the protein c-FLIP, a major factor of resistance to apoptosis, as a proof of concept. Accurate detection of endogenous c-FLIP levels in the preclinical settings is imperative since it is considered as a potential theranostic biomarker. Several sources of c-FLIP antibodies validated by their manufacturer and recommended for western blotting were therefore rigorously tested. We found a wide divergence in immune recognition properties. While these antibodies have been used in many publications, our results show that several of them failed to detect endogenous c-FLIP protein by Western blotting. Our results suggest that antibody validation standards are inadequate, and that systematic use of genetic knockdowns and/or knockouts to establish proof of specificity is critical, even for antibodies previously used in the scientific literature. Because antibodies are fundamental tools in both preclinical and clinical research, ensuring their specificity is crucial.

背景与目标： : 成功地将临床前研究的发现转化为有效的疗法在生物医学研究中至关重要。由于重复次数不足，基于细胞的和小鼠模型不足，缺乏临床前数据的稳健性和可重复性导致成功率低。抗体广泛用于临床前研究，特别是用于确定感兴趣组织 (包括肿瘤) 中潜在治疗靶标的表达，还用于鉴定疾病和/或治疗反应生物标志物。我们试图确定临床前研究中当前的抗体表征标准是否足以确保同行评审出版物中发现的数据的可靠性。为了解决这个问题，我们使用了检测蛋白c-FLIP (抗凋亡的主要因素) 作为概念的证明。临床前环境中内源性c-FLIP水平的准确检测势在必行，因为它被认为是潜在的肿瘤生物标志物。因此，对其制造商验证并推荐用于蛋白质印迹的c-FLIP抗体的几种来源进行了严格测试。我们发现免疫识别特性存在很大差异。尽管这些抗体已在许多出版物中使用，但我们的结果表明，其中一些未能通过Western印迹检测到内源性c-FLIP蛋白。我们的结果表明，抗体验证标准是不充分的，并且系统地使用基因敲除和/或敲除来建立特异性证明是至关重要的，即使对于以前在科学文献中使用的抗体也是如此。由于抗体是临床前和临床研究的基本工具，因此确保其特异性至关重要。

BACKGROUND & AIMS: :The strong link between gene expression of mitotic Aurora kinases and cancer has stimulated a very high interest in developing Aurora kinase inhibitors for cancer therapy. Validation of Aurora kinases as targets, and development of pharmacodynamic biomarkers for inhibitors of Aurora kinases, provides an example of how target validation can help the drug discovery process, and also of how to interpret results depending on the technology used. In this review, we outline the principal tools, concepts, and strategies of target and biomarker validation for Aurora kinases, with emphasis on validation results derived from RNA-interference experiments. These data were essential for the decision to enter the next steps in drug development and for the selection of the appropriate biomarkers for clinical trials.

背景与目标： : 有丝分裂极光激酶的基因表达与癌症之间的紧密联系激发了人们对开发用于癌症治疗的极光激酶抑制剂的高度兴趣。Aurora激酶作为靶标的验证以及Aurora激酶抑制剂的药效学生物标志物的开发，提供了靶标验证如何帮助药物发现过程以及如何根据所使用的技术解释结果的示例。在这篇综述中，我们概述了Aurora激酶的靶标和生物标志物验证的主要工具，概念和策略，重点是RNA干扰实验得出的验证结果。这些数据对于决定进入药物开发的下一步以及为临床试验选择合适的生物标志物至关重要。