A Comparison of the Accuracy of Clinician Prediction of Survival Versus the Palliative Prognostic Index

Context

Survival predictions for advanced cancer patients impact many aspects of care, but the accuracy of clinician prediction of survival (CPS) is low. Prognostic tools such as the Palliative Prognostic Index (PPI) have been proposed to improve accuracy of predictions. However, it is not known if PPI is better than CPS at discriminating survival.

Interestingness measures and strategies for mining multi-ontology multi-level association rules from gene ontology annotations for the discovery of new GO relationships

The Gene Ontology (GO), a set of three sub-ontologies, is one of the most popular bio-ontologies used for describing gene product characteristics. GO annotation data containing terms from multiple sub-ontologies and at different levels in the ontologies is an important source of implicit relationships between terms from the three sub-ontologies. Data mining techniques such as association rule mining that are tailored to mine from multiple ontologies at multiple levels of abstraction are required for effective knowledge discovery from GO annotation data. We present a data mining approach, Multi-ontology data mining at All Levels (MOAL) that uses the structure and relationships of the GO to mine multi-ontology multi-level association rules. We introduce two interestingness measures: Multi-ontology Support (MOSupport) and Multi-ontology Confidence (MOConfidence) customized to evaluate multi-ontology multi-level association rules. We also describe a variety of post-processing strategies for pruning uninteresting rules. We use publicly available GO annotation data to demonstrate our methods with respect to two applications (1) the discovery of co-annotation suggestions and (2) the discovery of new cross-ontology relationships.     

Optical Bandgap Definition via a Modified Form of Urbach’s Rule

We are reporting an esoteric method to determine the optical bandgap of direct gap materials by employing Urbach’s rule. The latter, which describes the slope of the band tail absorption in semiconductors, in its original version, cannot be employed to pinpoint the optical bandgap. Herein, however, we show that a modified form of Urbach’s rule defines the optical bandgap, and therefore, enables the accurate determination of the optical bandgap energy, which turns out to be identical with the threshold energy for the band tail absorption. The model further produces an explicit expression for the absorption coefficient at the optical bandgap energy.     

从肿瘤基因表达数据挖掘分类规则的研究

基于肿瘤基因表达数据,利用信息科学的方法和技术建立肿瘤预测分类模型,对肿瘤基因表达模式研究和肿瘤的诊断识别具有重要意义.本研究提出一种从肿瘤基因表达数据中直接挖掘分类规则建立肿瘤预测分类器的方法.该方法首先抽取实验样本集,分别找出标记肿瘤和正常组织样本的分类特征,由此生成可预测样本类别的分类规则,对每个未知类别样本,按照置信度最高原则,选择一个分类规则作为预测结构.本研究的实验数据来自Broad Institute的前列腺癌基因表达数据,实验结果显示该方法的预测精度在90%以上,且同时获得了大量结构透明的分类预测规则,表明本研究的方法是可行的和有效的.     

“大气一转其气乃散”临床应用探析

文章根据"大气一转,其气乃散"的原则,指出大气当是气机正常流动的一种状态,并从上焦之宗气、中焦之脾胃中气,下焦之肾中元气,以及阴阳交接的厥阴肝气四方面详细论述,提出运转大气不仅是治疗水气病的重要原则,对于现代临床中多种疾病的治疗也有重要的指导意义。     

应用国际血细胞复检规则中可疑警示条款筛查初诊白血病的探讨

目的Beckman Coulter LH755血液分析仪显示的形态学可疑警示信息结合国际血细胞复检规则中相应条款,探讨其用于初诊白血病筛查的价值,为制定本室血细胞复检规则提供依据。方法1984例患者标本分为初诊非白血病组（1832例）,初诊白血病组（73例）和复诊组（79例）,所有标本同时进行仪器分析和手工白细胞分类及细胞形态观察,参照国际复检规则,对初诊非白血病组和A血病组标本涉及的国际血细胞可疑警示条款进行评价,观察白血病和非白血病患者治疗前后变化;运用受试者工作特征（ROC）曲线,观察其对初诊白血病筛查的价值。结果本组初诊病例724例涉及可疑警示条款,其中非白血病组655例,白血病组69例,46例髓系白血病均涉及可疑警示条款,且显微镜镜检阳性;其中条款34（左移报警）和37（原始细胞报警）,敏感性和阳性预期值均较高,条款30[血小板（PLT）聚集报警],31（PLT报警）和35[不典型和（或）变异Lym]阳性预期值较低;治疗后患者检出假阴性病例28例,其中8例检出原始细胞,这些标本均来自于白血病治疗后患者（28．57％,8／28）;采用ROC曲线分析,条款37（原始细胞报警）对初诊白血病价值最高（AUC=0．821）,其次为条款34（左移报警）,32（IG报警）,26（白细胞结果不可靠）和35[不典型和（或）变异Lym],而条款30（PLT聚集报警）和31（PLT报警）诊断价值较小。结论参照国际血细胞复检可疑警示条款对于初诊白血病筛查有重要价值,白血病患者治疗后细胞形态更为多样和复杂,仪器示警不能直接提供血细胞形态变化的确切信息,需进一步用显微镜镜检血涂片进行核实;当标本涉及条款37（原始细胞报警）时应予以显微镜镜检,以排除白血病可能,涉及条款26（白细胞结果不可靠）,32（IG报警）,34（左移报警）,35[不典型和（或）变异Lym]时也应引起重视,以免造成漏诊和误诊．     

Prospective comparison of three validated prediction rules for prognosis in community-acquired pneumonia

PURPOSE: We assessed the performance of 3 validated prognostic rules in predicting 30-day mortality in community-acquired pneumonia: the 20 variable Pneumonia Severity Index and the easier to calculate CURB (confusion, urea nitrogen, respiratory rate, blood pressure) and CURB-65 severity scores. SUBJECTS AND METHODS: We prospectively followed 3181 patients with community-acquired pneumonia from 32 hospital emergency departments (January-December 2001) and assessed mortality 30 days after initial presentation. Patients were stratified into Pneumonia Severity Index risk classes (I-V) and CURB (0-4) and CURB-65 (0-5) risk strata. We compared the discriminatory power (area under the receiver operating characteristic curve) of these rules to predict mortality and their accuracy based on sensitivity, specificity, predictive values, and likelihood ratios. RESULTS: The Pneumonia Severity Index (risk classes I-III) classified a greater proportion of patients as low risk (68% [2152/3181]) than either a CURB score <1 (51% [1635/3181]) or a CURB-65 score <2 (61% [1952/3181]). Low-risk patients identified based on the Pneumonia Severity Index had a slightly lower mortality (1.4% [31/2152]) than patients classified as low-risk based on the CURB (1.7% [28/1635]) or the CURB-65 (1.7% [33/1952]). The area under the receiver operating characteristic curve was higher for the Pneumonia Severity Index (0.81) than for either the CURB (0.73) or CURB-65 (0.76) scores (P <0.001, for each pairwise comparison). At comparable cut-points, the Pneumonia Severity Index had a higher sensitivity and a somewhat higher negative predictive value for mortality than either CURB score. CONCLUSIONS: The more complex Pneumonia Severity Index has a higher discriminatory power for short-term mortality, defines a greater proportion of patients at low risk, and is slightly more accurate in identifying patients at low risk than either CURB score.     

Adaptive evolution toward larger size in mammals

The notion that large body size confers some intrinsic advantage to biological species has been debated for centuries. Using a phylogenetic statistical approach that allows the rate of body size evolution to vary across a phylogeny, we find a long-term directional bias toward increasing size in the mammals. This pattern holds separately in 10 of 11 orders for which sufficient data are available and arises from a tendency for accelerated rates of evolution to produce increases, but not decreases, in size. On a branch-by-branch basis, increases in body size have been more than twice as likely as decreases, yielding what amounts to millions and millions of years of rapid and repeated increases in size away from the small ancestral mammal. These results are the first evidence, to our knowledge, from extant species that are compatible with Cope’s rule: the pattern of body size increase through time observed in the mammalian fossil record. We show that this pattern is unlikely to be explained by several nonadaptive mechanisms for increasing size and most likely represents repeated responses to new selective circumstances. By demonstrating that it is possible to uncover ancient evolutionary trends from a combination of a phylogeny and appropriate statistical models, we illustrate how data from extant species can complement paleontological accounts of evolutionary history, opening up new avenues of investigation for both.The idea that large size confers some intrinsic advantage has lingered in the psyche of biologists for centuries. Researchers have proposed that bigger body sizes can increase tolerance to environmental extremes (1), reduce mortality (2), and enhance predation success (3), among other advantages. In support of these conjectures, analyses from a range of different taxonomic groups demonstrate that larger individuals within populations have significantly enhanced survival, fecundity, and mating success (4, 5). If these advantages are general and have played out over long time scales, they could explain the existence of Cope’s rule (6): a broad trend toward increasing size through time (4, 5, 7).Mammals evolved from a relatively small common ancestor over 165 Ma (8–10) and went on to form one of the largest and most successful vertebrate radiations in Earth’s history. Mammals vary greatly in size, spanning almost eight orders of magnitude. This variation implies that some groups have experienced much greater evolutionary change in size from the ancestral form than others. Indeed, the mammalian fossil record provides the clearest evidence in support of Cope’s rule over long evolutionary time scales (6, 11, 12).Despite the paleontological support, evidence for Cope’s rule remains elusive from studies of extant data alone (13–15), including studies of the mammals (16). A possible reason for the discrepancy between paleontological and extant data might be that conventional comparative methods for studying trends within extant data implicitly assume homogeneous evolutionary patterns and processes. When these assumptions are violated, it renders the homogeneous modeling approach incomplete at best and at worst, a source of potential bias in the study of historical evolutionary change; for example, reconstructions of probable ancestral values can be biased toward average or intermediate values (17, 18), which would thereby mask long-term evolutionary trends that are apparent from the fossil record.Previously, we have shown that rates of body size evolution in mammals routinely violate the assumption of homogeneity (19), but how these rate changes might be related to size itself has not been studied. If changes toward larger size in the mammals have consistently occurred at rates that differ from changes toward smaller size, then reconstructed ancestral states accounting for these rate differences may track more closely the observed fossil record. Such a pattern would allow the detection of size-related evolutionary trends from extant data (Fig. S1).Here, we apply a statistical phylogenetic approach for reconstructing mammalian evolutionary history that allows the rate of evolution to vary throughout a phylogenetic tree without prior knowledge or specification of where and when rate shifts occurred. We use this method to test for size-related biases in rates of morphological change and ask whether accounting for any such bias allows us to predict a generalized pattern of size increase in the mammals in line with the generalized pattern of size increase observed in the fossil record. Finally, we consider whether a size-related bias in the rate of morphological evolution can help to choose among the several macroevolutionary processes that have been suggested to give rise to Cope’s rule.     

Revisions to USDA biotechnology regulations: The SECURE rule

In keeping with the directive in Executive Order 13874 (Modernizing the Regulatory Framework for Agricultural Biotechnology Products) to adopt regulatory approaches that are proportionate to risk and avoid arbitrary distinctions across like products, the US Department of Agriculture (USDA) revised its biotechnology regulations by promulgating the Sustainable, Ecological, Consistent, Uniform, Responsible, and Efficient (SECURE) rule. Specifically, the SECURE rule 1) establishes exemptions for plants modified by genetic engineering where the modification could otherwise have been made through conventional breeding, 2) uses risk posed by the introduced trait to determine whether an organism is regulated, rather than relying on whether the organism was developed using a plant pest, and 3) provides a mechanism for a rapid initial review to efficiently distinguish plants developed using genetic engineering that do not pose plausible pathways to increased plant pest risk from those that do. As a result of the focused oversight on potentially riskier crops developed using genetic engineering, USDA is expected to improve the efficiency and effectiveness of its oversight program. The reduced regulatory burden is expected to promote innovation by expanding the number and diversity of developers to include smaller businesses and academics and to increase the number and variety of traits being developed through biotechnology.     

Quantitative visualization of passive transport across bilayer lipid membranes

The ability to predict and interpret membrane permeation coefficients is of critical importance, particularly because passive transport is crucial for the effective delivery of many pharmaceutical agents to intracellular targets. We present a method for the quantitative measurement of the permeation coefficients of protonophores by using laser confocal scanning microscopy coupled to microelectrochemistry, which is amenable to precise modeling with the finite element method. The technique delivers well defined and high mass transport rates and allows rapid visualization of the entire pH distribution on both the cis and trans side of model bilayer lipid membranes (BLMs). A homologous series of carboxylic acids was investigated as probe molecules for BLMs composed of soybean phosphatidylcholine. Significantly, the permeation coefficient decreased with acyl tail length contrary to previous work and to Overton's rule. The reasons for this difference are considered, and we suggest that the applicability of Overton's rule requires re-evaluation.