Causal Diagram Techniques for Urologic Oncology Research

Large quantities of data are now available to medical researchers; however, observational studies are plagued by bias and confounding. Additionally, much of this research only speculates on variable associations, leaving prospective randomized clinical trials as the sole purveyors of claims about causal relations between variables. There has been a growing movement of causal inference that uses new techniques to investigate causality using observational data. These techniques include the implementation of directed acyclic graphs, which allow researchers to explicitly and reproducibly define the causal relationships between study variables, thus making statistical analysis more robust. Directed acyclic graphs further allow researchers to identify confounding and other sources of bias and to discover causal effects among complex networks of variables. This review aims to introduce these techniques to the general urology and urologic oncology research communities in order to provide a basic understanding of causal inference and analysis and call for integration of these practices more generally in research methodology.     

Learning from nature – Novel synthetic biology approaches for biomaterial design

Many biomaterials constructed today are complex chemical structures that incorporate biologically active components derived from nature, but the field can still be said to be in its infancy. The need for materials that bring sophisticated properties of structure, dynamics and function to medical and non-medical applications will only grow. Increasing appreciation of the functionality of biological systems has caused biomaterials researchers to consider nature for design inspiration, and many examples exist of the use of biomolecular motifs. Yet evolution, nature’s only engine for the creation of new designs, has been largely ignored by the biomaterials community. Molecular evolution is an emerging tool that enables one to apply nature’s engineering principles to non-natural situations using variation and selection. The purpose of this review is to highlight the most recent advances in the use of molecular evolution in synthetic biology applications for biomaterial engineering, and to discuss some of the areas in which this approach may be successfully applied in the future.     

日本血吸虫(中国大陆株)表达基因的分离和EST序列测定

目的 运用表达标签技术（ＥＳＴ方法）,从ＳｊｃＤＮＡ文库中分离、鉴定血吸虫表达基因序列。方法 应用ＥＳＴ方法,人ＳｊｃＤＮＡ文库中随机挑出单个重组克陲 ＰＣＲ直接序列分析,通过互联网将获得的ＥＳＴ序列送入ＮＣＢＩＧｅｎＢａｎｋ进行同源性检素,并将发现的未知基因ＥＳＴ序列送入ＮＣＢＩｄｂＥＳＴ以获得ＧｅｎＢａｎｋ进入号。结果 分离了１００个ＳｊＧｅｎＢａｎｋ中已知的血吸虫基因序列,１９个为未知基因序     

Neocortical seizure foci localization by means of a directed transfer function method

Purpose: Determination of the origin of extratemporal neocortical onset seizures is often challenging due to the rapid speed at which they propagate throughout the cortex. Typically, these patients are poor surgical candidates and many times experience recurrences of seizure activity following resection of the assumed seizure focus. Methods: We applied a causal measurement technique—the directed transfer function (DTF)—in an effort to determine the cortical location responsible for the propagation of the seizure activity. Intracranial seizure recordings were obtained from a group of 11 pediatric patients with medically intractable neocortical‐onset epilepsy. Time windows were selected from the recordings following onset of the ictal activity. The DTF was applied to the selected time windows, and the frequency‐specific statistically significant source activity arising from each cortical recording site was quantified. The DTF‐estimated source activity was then compared with the seizure‐onset zone(s) identified by the epileptologists. Results: In an analysis of the 11 pediatric patients, the DTF was shown to identify estimated ictal sources that were highly correlated with the clinically identified foci. In addition, it was observed that in the patients with multiple ictal foci, the topography of the casual source activity from the analyzed seizures was associated with the separate clinically identified seizure‐onset zones. Discussion: Although localization of neocortical‐onset seizures is typically challenging, the causal measures employed in this study—namely the directed transfer function—identified generators of the ictal activity that were highly correlated with the cortical regions identified as the seizure‐onset zones by the epileptologists. This technique could prove useful in the identification of seizure‐specific propagation pathways in the presurgical evaluation of patients with epilepsy.     

Altered patterns of directed connectivity within the reading network of dyslexic children and their relation to reading dysfluency

Reading is a complex cognitive skill subserved by a distributed network of visual and language-related regions. Disruptions of connectivity within this network have been associated with developmental dyslexia but their relation to individual differences in the severity of reading problems remains unclear. Here we investigate whether dysfunctional connectivity scales with the level of reading dysfluency by examining EEG recordings during visual word and false font processing in 9-year-old typically reading children (TR) and two groups of dyslexic children: severely dysfluent (SDD) and moderately dysfluent (MDD) dyslexics. Results indicated weaker occipital to inferior-temporal connectivity for words in both dyslexic groups relative to TRs. Furthermore, SDDs exhibited stronger connectivity from left central to right inferior-temporal and occipital sites for words relative to TRs, and for false fonts relative to both MDDs and TRs. Importantly, reading fluency was positively related with forward and negatively with backward connectivity. Our results suggest disrupted visual processing of words in both dyslexic groups, together with a compensatory recruitment of right posterior brain regions especially in the SDDs during word and false font processing. Functional connectivity in the brain’s reading network may thus depend on the level of reading dysfluency beyond group differences between dyslexic and typical readers.     

研究设计时混杂控制策略的结构分类

混杂影响着人群因果关系的发生。依据混杂因素是否已知、可测量及已测量,可将其分为4类情形。基于有向无环图,对混杂的控制策略分为两类：①混杂路径打断法,又可分为单路径和双路径打断法,分别对应于暴露完全干预法、限制法和分层法;②混杂路径保留法,分别对应于暴露不完全干预法（工具变量设计或不完美的随机对照试验）、中间变量法和匹配法。其中,随机对照试验、工具变量设计或孟德尔随机化设计、中间变量分析可满足4类混杂的控制,而限制法、分层法和匹配法仅适用于已知、可测量并已测量的混杂。识别不同类型混杂的控制机制,有助于在研究设计阶段提出应对措施,是获得正确因果效应估计的前提。     

Agent Based Modeling of “Crowdinforming” as a Means of Load Balancing at Emergency Departments

This work extends ongoing development of a framework for modeling the spread of contact-transmission infectious diseases. The framework is built upon Agent Based Modeling (ABM), with emphasis on urban scale modelling integrated with institutional models of hospital emergency departments. The method presented here includes ABM modeling an outbreak of influenza-like illness (ILI) with concomitant surges at hospital emergency departments, and illustrates the preliminary modeling of ‘crowdinforming’ as an intervention. ‘Crowdinforming’, a component of ‘crowdsourcing’, is characterized as the dissemination of collected and processed information back to the ‘crowd’ via public access. The objective of the simulation is to allow for effective policy evaluation to better inform the public of expected wait times as part of their decision making process in attending an emergency department or clinic. In effect, this is a means of providing additional decision support garnered from a simulation, prior to real world implementation. The conjecture is that more optimal service delivery can be achieved under balanced patient loads, compared to situations where some emergency departments are overextended while others are underutilized. Load balancing optimization is a common notion in many operations, and the simulation illustrates that ‘crowdinforming’ is a potential tool when used as a process control parameter to balance the load at emergency departments as well as serving as an effective means to direct patients during an ILI outbreak with temporary clinics deployed. The information provided in the ‘crowdinforming’ model is readily available in a local context, although it requires thoughtful consideration in its interpretation. The extension to a wider dissemination of information via a web service is readily achievable and presents no technical obstacles, although political obstacles may be present. The ‘crowdinforming’ simulation is not limited to arrivals of patients at emergency departments due to ILI; it applies equally to any scenarios where patients arrive in any arrival pattern that may cause disparity in the waiting times at multiple facilities.