Preclinical safety evaluations supporting pediatric drug development with biopharmaceuticals: strategy,challenges, current practices

Evaluation of pharmaceutical agents in children is now conducted earlier in the drug development process. An important consideration for this pediatric use is how to assess and support its safety. This article is a collaborative effort of industry toxicologists to review strategies, challenges, and current practice regarding preclinical safety evaluations supporting pediatric drug development with biopharmaceuticals. Biopharmaceuticals include a diverse group of molecular, cell‐based or gene therapeutics derived from biological sources or complex biotechnological processes. The principles of preclinical support of pediatric drug development for biopharmaceuticals are similar to those for small molecule pharmaceuticals and in general follow the same regulatory guidances outlined by the Food and Drug Administration and European Medicines Agency. However, many biopharmaceuticals are also inherently different, with limited species specificity or immunogenic potential which may impact the approach taken. This article discusses several key areas to aid in the support of pediatric clinical use, study design considerations for juvenile toxicity studies when they are needed, and current practices to support pediatric drug development based on surveys specifically targeting biopharmaceutical development. Birth Defects Res (Part B) 92:359–380, 2011. © 2011 Wiley‐Liss, Inc.     

Nature reserve group planning for conservation of giant pandas in North Minshan, China

Formation of nature reserve groups (NRGs) is an important approach for optimising spatial patterns in nature reserves and for improving the efficiency of nature reserve networks. In this study, based on habitat evaluation and connectivity analysis, the approach and method for optimising spatial patterns and functional zoning of reserves were analysed using the case study of giant panda (Ailuropoda melanoleuca) reserves in North Minshan. Results indicated that five panda nature reserves had been established, which formed a reserve group and covered 48.4% of panda habitat and three of five population components. Although the nature reserves were connected to each other, core zones were divided into seven isolated areas. These divisions can reduce the efficiency of protecting giant pandas in reserve systems. To optimise spatial patterns in nature reserves, one new reserve is proposed and it is recommended that core zones be expanded and merged into two areas, in accordance with the spatial distribution of the panda population. Three linkage areas are also proposed—for facilitating panda exchange and movement among different populations. The study is expected to provide a scientific basis for planning the development of nature reserves in this mountain range, to promote the establishment of nature reserve groups in other areas, and to optimise entire nature reserve systems in China.     

高分辨MSCT薄层重组在常规胸部体检中的应用

目的：探讨多排螺旋CT（MSCT）高分辨薄层重组对体检中肺部疾病的诊断价值,以及MSCT薄层重组与常规CT扫描图像质量及诊断准确率对照。方法：搜集做64排常规CT扫描同时行薄层重组的2473例体检病例中筛选的97例患者进行回顾性分析。结果：97例患者在常规CT扫描中有80例可以显示病变,而在MSCT薄层重组中97例均有阳性发现;其中双肺弥漫性病变79例（两肺间质纤维化78例,肺内多发转移瘤1例）,肺结核3例,肺内孤立结节12例,早期中央型肺癌1例,先天性支气管闭锁1例以及纵隔肿瘤1例;MSCT薄层重组图像可清晰显示肺内小叶间隔线增厚、弥漫分布的囊性病变、肺内结节的细微征象。结论：MSCT薄层重组在胸部体检中的诊断阳性率、细节分辨率、图像质量及确诊率均优于常规CT,可作为肺内病变尤其是早期肺癌筛查方法之首选。     

石墨化炭/炭复合材料＋羟基磷灰石涂层（C/C＋HA）复合骨植入材料研究

目的：通过建立兔股骨缺损的动物实验模型,对采用等温化学气相沉积法和等离子喷涂技术所制备的石墨化炭/炭复合材料＋羟基磷灰石涂层（C/C＋HA）复合骨植入材料进行骨植入实验的的生物相容性进行评价,探索该复合材料作为植入机体骨组织的可行性依据。方法：采用骨科钻在实验动物股骨髁上钻孔的方法建立骨缺损的动物实验模型,将待研究比较的实验材料分别植入实验动物的股骨髁内,持续观察8周,在术后第2、4、8周时应用X线照片、组织学染色和扫描电镜技术,分别观察所研究材料在机体内对骨缺损愈合及其对机体的影响,进行组间比较和相关性分析。结果：石墨化炭/炭复合材料＋羟基磷灰石涂层（C/C＋HA）复合骨植入材料的骨植入实验生物相容性良好,材料与骨组织结合牢固,界面中成骨细胞生长明显,且炭颗粒脱落现象少,未见炎症细胞浸润。植入动物体内的材料在植入期未引起机体局部的炎症浸润反应且表面脱落的碳颗粒在机体组织中也未引起局部严重的炎症反应。在实验动物植入材料后的连续8周观察期中,组织学观察显示：表面涂有HA的炭/炭复合材料对骨组织形态改建上表现良好,其与骨组织接界处所形成的纤维结缔组织膜层厚度明显比未涂HA的材料要小,与骨组织结合更为紧密和牢固;碳颗粒出现脱落游离的现象明显减少。结论：在炭/炭复合材料表面涂以HA生物涂层对骨的形态改建和促进骨小梁生长等方面具有良好的作用,是一种具有发展潜力的骨修复材料。     

Fox‐baiting in agricultural landscapes in south‐eastern Australia: a case‐study appraisal and suggestions for improvement

Summary In south‐eastern Australia, the introduced Red Fox (Vulpes vulpes) is a major predator of native wildlife and livestock. Fox control in agricultural landscapes is heavily reliant on the laying of poisoned baits by private landholders, yet there have been few assessments of the application or success of landholder‐baiting practices. We evaluated a community‐based fox‐baiting campaign, typical of programs employed throughout the agricultural regions of south‐eastern Australia to control foxes. We recorded the spatial coverage of 1080 baits deployed by landholders, assessed baiting procedures, monitored the survival of six radio‐collared foxes during and after baiting, and compared the spatial coverage and likely effectiveness of the baiting program with two alternative (theoretical) baiting strategies. Relative to other baiting programs, coordination among neighbours was reasonably high, with 37.5% of baited properties (n = 40) adjoining ≥3 neighbouring properties that also contained baits. Nevertheless, the maximum distance from the centre of a baited property to the nearest edge of an unbaited property was <750 m (mean = 380 m ± 147 m SD). On average, 33% (±17% SD) of each fox’s home range overlapped with baited properties, but only two foxes died during the baiting program. The remaining four foxes were still alive 10 weeks after baiting ceased. Modelling of simulated fox home ranges showed that 13.5% contained no bait stations based on the community baiting program, whereas alternative roadside‐ and grid‐baiting strategies (theoretically) delivered baits to all simulated home ranges. Some landholders employed practices that could reduce the effectiveness of baiting programs such as not removing decayed baits before deploying new ones or placing bait stations too close together. Our research illustrates the difficulties of managing a coordinated baiting program on private land that effectively controls foxes. Alternative baiting strategies such as roadside baiting need to be considered to improve fox control in agricultural landscapes.     

转基因植物环境安全评价策略

构建完善的转基因植物环境安全评价技术体系是保障转基因生物产业健康发展的重要组成部分。本文综述了转基因植物环境安全评价技术发展历程与趋势,归纳了转基因植物环境安全评价的思路与内容。转基因植物环境安全评价应分为潜在风险分析、风险假设验证、风险特征描述等3个步骤,并采用逐层评价模式;安全评价应贯穿转基因植物新品种研发与产业化全程,包括应用前预测、研发中筛选、推广前评价、推广后监测。此外,基于科学性和个案分析原则,本文对复合性状、非生物胁迫抗性等新型转基因植物环境安全评价策略进行了探讨。     

Study on coastal wetland habitat quality evaluation in Quanzhou Bay, Fujian, China

Coastal wetland is located in the active interface between land and sea, which is one of the richest biodiversity habitats, while it is seriously disturbed and destroyed by anthropogenic activities in both terrestrial and marine parts. Habitat serves as the basis for organism survival, providing food, shelter, water, space and so on, and habitat degradation and loss caused by intense anthropogenic activities is widely considered as the main reason for biodiversity decline and loss. However, there is still limited study on the evaluating methods of coastal wetland habitats, especially for those in a large scale. In this study, methods for evaluating coastal wetland habitat quality, including selecting indicators, setting value assignment criteria and weights were discussed systematically, a method of coastal wetland habitat quality evaluation was established, and the habitat quality in Quanzhou Bay was also evaluated as a case study. The present study provided a new concept and method to assess quantitatively habitat status, indicate the ecological status and its change, and also reflect and predict indirectly the ecological impact of human activities.
Referring to the habitat evaluation system (HES) developed by United States in the mid 1970s, the evaluation method was established by thorough analysis of the characteristics of coastal wetland. The habitat indicators were selected in terms of three habitat factors as follows: chemical factors, including dissolved oxygen (DO), phosphate in seawater, sulfide in sediment, and regional priority pollutants; physical factors, including landscape naturalness index and coastline artificialization index; biological factors, including invasive species risk and area ratio of invasive alien species. Weights were established by Analytic Hierarchy Process, combined with several-round expert evaluation. Evaluation criteria providing principles for value assignment of each indicator, were established referring to previous standards and related researches. The final result for assessing habitat quality was indicated and stated by the value of Habitat Quality Index (HQI), which is the weighted sum of each indicator. Habitat quality increased with the HQI value, with value ranging from 0 to 100.
The established evaluating method was applied to assess the habitat quality of Quanzhou Bay, located in the southeast coastal zone of Fujian Province, with a total area of 136.4 km², which is an important bay in Fujian. Quanzhou Bay wetland is a typical coastal wetland with diverse wetland habitats, including mangrove, estuary, island, aquaculture ponds, salt pan, shallow sea, mud flat and so on. The Quanzhou Bay is now seriously suffering environmental problems, e.g. eutrophication due to great discharge of domestic, agricultural and industrial wastewater, rapid urbanization and reclamation resulting in decreased wetland area, and the invasion of alien species. The evaluation results showed that the habitat quality index value was 68.13, 57.99 and 51.23 in 1989, 2002 and 2008, respectively, indicating that the habitat degraded gradually. The five major factors that led to decline of HQI value were phosphate in seawater, lead in sediment, landscape naturalness index and coastline artificialization index and area ratio of invasive alien species. Therefore, in order to improve and maintain habitat quality, it is urgent to control pollution, large-scale reclamation and Spartina invasion in Quzhou Bay.     

急性生理功能和慢性健康状况评分在医院感染目标性监测中的意义

急性生理功能和慢性健康状况评分不仅对评估ICU患者的预后有着重要作用,而且在医院感染目标性监测中起到不可或缺的作用。综述了这方面的最新研究进展,旨在推荐在医院感染目标性监测中用急性生理功能和慢性健康状况评分评估患者病情严重程度,用其调整ICU目标性监测的医院感染发生率,为各家医院比较医院感染发生率提供客观、统一的评价标准。     

Risk Assessment and Class-Based Evaluation of Three Phosphate Esters

A category approach was used in the evaluation of a group of chemicals (triethyl phosphate, tripropyl phosphate, and tributyl phosphate) in drinking water, in support of determination of safe-harbor level for use by a standard-setting organization. Both non-cancer and cancer endpoints were considered, and risk assessment methodology developed by the U.S. Environmental Protection Agency (USEPA) was used to determine a class-based evaluation level (CBEL) and a total allowable concentration (TAC) in drinking water considered adequately protective of human health. The critical study was a chronic oncogenicity study on tributyl phosphate, with a no-observed-adverse-effect-level (NOAEL) of 9 mg/kg-day. The critical effect, combined incidence of bladder papilloma/transitional cell carcinoma, was likely non-genetic in nature, as supported by the lack of genetic toxicity observed in tributyl phosphate. The effect thus demonstrated a threshold, and this study used an oral reference dose approach and a total uncertainty factor of 100. This conservative analysis demonstrated the TAC should be twenty times greater than the default value of 0.01 mg/L.     

汉江中下游浮游植物群落结构及水质评价

南水北调中线工程调水后,汉江中下游水华频发引起社会关注。为掌握调水后汉江中下游浮游植物的群落结构特征,于2017年11月、2018年2月、4月和8月在汉江中下游的8个断面对浮游植物进行了定量调查。调查结果显示:共鉴定浮游植物163种,群落组成以硅藻门(Bacillariophyta)、绿藻门(Chlorophyta)为主,其次是蓝藻门(Cyanophyta)。浮游植物优势种主要为硅藻门的梅尼小环藻(Cyclotella meneghiniana)、颗粒直链藻最窄变种(Melosira granulata var.)、变异直链藻(Melosira varians)、颗粒直链藻(Melosira granulata),隐藻门的卵形隐藻(Cryptomonas ovata),蓝藻门的弯曲颤藻(Oscillatoria sp.)和伪鱼腥藻(Pseudoanabaena sp.),且都有较高的优势度。浮游植物密度和生物量的季节变化范围分别为0. 33×106cells/L～1. 82×106cells/L和0. 49 mg/L～7. 38 mg/L。基于Shannon-Weaver多样性指数和Pielou均匀度指数以及优势种评价法对汉江中下游的水质进行评价,判断汉江中下游水质整体处于中污状态。