Using real-world data to predict health outcomes—The prediction design: Application and sample size planning

The gold standard for investigating the efficacy of a new therapy is a (pragmatic) randomized controlled trial (RCT). This approach is costly, time-consuming, and not always practicable. At the same time, huge quantities of available patient-level control condition data in analyzable format of (former) RCTs or real-world data (RWD) are neglected. Therefore, alternative study designs are desirable. The design presented here consists of setting up a prediction model for determining treatment effects under the control condition for future patients. When a new treatment is intended to be tested against a control treatment, a single-arm trial for the new therapy is conducted. The treatment effect is then evaluated by comparing the outcomes of the single-arm trial against the predicted outcomes under the control condition. While there are obvious advantages of this design compared to classical RCTs (increased efficiency, lower cost, alleviating participants’ fear of being on control treatment), there are several sources of bias. Our aim is to investigate whether and how such a design—the prediction design—may be used to provide information on treatment effects by leveraging external data sources. For this purpose, we investigated under what assumptions linear prediction models could be used to predict the counterfactual of patients precisely enough to construct a test and an appropriate sample size formula for evaluating the average treatment effect in the population of a new study. A user-friendly R Shiny application (available at: https://web.imbi.uni-heidelberg.de/PredictionDesignR/ ) facilitates the application of the proposed methods, while a real-world application example illustrates them.     

昆虫发育进度的非正态描述──分段指数曲线

提出了分段连续指数曲线转化为多元线性回归方程的方法。利用取剩余平方和最小的方法确定未知折点。给出了在描述昆虫发育进度的模拟模型。     

Key taste components in two wild edible Boletus mushrooms using widely targeted metabolomics

Compounds from wild edible mushrooms has been reported to exert biological activities and contribute to the different flavors of mushrooms in our diet. Wild edible Boletus mushrooms are popular in Southwest China. In this study, we performed ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) based on widely targeted metabolomics analysis to identify key components. A total of 194 metabolites (113 upregulated, 81 downregulated) divided into 11 groups (49 metabolites in group lipids, 34 in amino acids and derivatives, 30 in organic acids, 18 in phenolic acids, 16 in nucleotides and derivatives, 13 in alkaloids, 6 in flavonoids, 3 in lignans and coumarins, 3 in tannins, 2 in terpenoids, and 20 in others) were found among Boletus bainiugan compared with B. subsplendidus. Through clustering analysis, principal component analysis (PCA), and orthogonal signal correction and partial least squares-discriminant analysis (OPLS-DA), different metabolites from fruiting bodies were clearly identified. Significant differences were observed in the metabolites between Boletus bainiugan and B. subsplendidus. These metabolites are involved in important biological functions. Our results provide new insights into important metabolites and theoretical basis for the taste difference of two wild edible Boletus mushrooms.     

茶园害虫匮乏期天敌与蚊虫的空间关系

为了充分发挥中性昆虫蚊虫作为天敌的食饵替代物作用,科学地保护和利用自然天敌,2015年和2016年开展了合肥地区白毫早茶园和乌牛早茶园害虫匮乏时期(3—5月)的天敌与蚊虫之间的空间关系研究,运用地学统计学方法求得天敌和蚊虫各自的变程,用灰色关联度方法分析蚊虫与天敌变程的关联度,关联度值越大的天敌在空间上对蚊虫的跟随关系越密切。并分析茶树品种间及年度间天敌位次的变化。8种天敌中,白毫早茶园2015年与蚊虫空间跟随关系密切的前四位天敌是粽管巢蛛、八斑球腹蛛、三突花蟹蛛和茶色新圆蛛;2016年的是粽管巢蛛、茶色新圆蛛、锥腹肖蛸和三突花蟹蛛;两年间前四位天敌有3种相同,但位次不全相同。乌牛早茶园2015年与蚊虫空间跟随关系密切的前四位天敌是八斑球腹蛛、茶色新圆蛛、锥腹肖蛸和三突花蟹蛛;2016年的是三突花蟹蛛、粽管巢蛛、草间小黑蛛和茶色新圆蛛;两年间前四位天敌中有茶色新圆蛛和三突花蟹蛛2种相同。年度间天敌位次相异率为87.5%,茶树品种间天敌位次相异率为93.75%。按照天敌位次总和及按照天敌与蚊虫空间关系密切指数总和评判,两种茶园2015年和2016年3—5月份与蚊虫空间关系密切的前四位天敌均依次是粽管巢蛛、三突花蟹蛛、茶色新圆蛛和八斑球腹蛛。本文的结果为人为地促进优势种天敌建群,合理保护和利用自然天敌提供科学依据。     

漓江流域生态系统服务价值最大化的土地利用结构优化

土地利用结构优化是促进生态系统可持续发展的重中之重,而生态管理的最终目标是优化生态系统服务,使生态系统提供的服务达到最大化。选择典型生态脆弱区漓江流域为研究区,将整个生态系统服务价值的最大化作为研究目标,首先结合野外实验和五期Landsat高分遥感影像获取基础数据,对研究区1998-2018年各项生态系统服务价值进行估算,然后结合灰色线性模型对2018-2028年价值进行预测,借助Lingo软件提出生态效益最大化的土地结构优化方案,进而对优化前后研究区生态系统服务价值进行比较与分析。结果表明：（1）近20年间研究区主要土地利用类型一直以林地与耕地为主,所占比例保持在整个流域的95%。水域与耕地面积逐年减少,林地、建设用地及未利用地面积持续增加。此外,未利用地面积发生的变化最为显著,增加了近30倍,主要由林地与耕地转变而来。（2）研究区生态系统服务价值总体约减少了19.55×10⁶元,呈现先上升后下降趋势,并将长期处于下降趋势,至2028年时流域生态系统服务价值将减少至8067.43×10⁶元。在流域整体生态系统中,林地价值最高,在历年约占流域总价值的86%,其次是水域及耕地,分别占比8%、6%。（3）对研究区进行优化后,漓江流域总生态系统服务价值增长了2%,其中主要来源于林地与水域面积的增加,提高了生态系统调节服务的供给能力,耕地、建设用地面积略微增加,未利用地面积显著减少,基本与2008年水平持平。本研究通过优化喀斯特地区关键生态系统服务价值,为该区域生态管理提供科学支撑。     

Infection Process of Botrytis cinerea on Eucalypt Leaves

This study aimed to elucidate the infection process of Botrytis cinerea on eucalypt leaves. Tests were conducted to evaluate the influence of leaf side (adaxial or abaxial), leaf age and luminosity on conidial germination, appressorium formation and grey mould (GM) severity. The adaxial and abaxial surfaces of detached eucalypt leaves were inoculated with a conidial suspension of B. cinerea and kept under constant light or dark. Subsequently, the adaxial surface of young and old leaves was inoculated and kept in the dark. To evaluate the percentage of conidia germination and appressorium formation, leaf samples were collected 6 hours after inoculation (hai), clarified (alcohol and chloral hydrate) and evaluated under a light microscope. The severity of GM was assessed 10 days after inoculation. For scanning electron microscopy analysis, samples were collected from 2 to 168 hai. A higher percentage of conidia germination (92%) and GM severity (21%) occurred on the adaxial surfaces of leaves kept in the dark. There was no statistical difference between the surfaces of young and old leaves for conidia germination. No appressorium was formed by B. cinerea. The GM severity on young leaves (17.3%) was 34 times higher than on old leaves (0.5%). The micrographs showed germinating conidia emitting 1–4 germ tubes in samples at 4 hai. The fungus penetration occurred through intact leaf surfaces, and both extra‐ and intracellular colonization of the mesophyll cells by the hyphae of the pathogen were observed at 120 hai. Sporulation occurred on the adaxial and abaxial surfaces (macronematous conidiophores) and below the epidermis (micronematous conidiophores).     

半定规划鲁棒不可行性研究

本文给出了一种判别半定规划鲁棒不可行的准则,通过该准则我们可判断模型对输入数据是否敏感,进而决定是否应该利用鲁棒优化建模的方法对模型进行重新建模,使其所求解具有鲁棒性.避免了所给模型在实际应用中存在较大的风险性,为更好的应用鲁棒优化建模方法提供了理论依据.     

胚乳性状数量基因的定位方法

将三倍体胚乳性状的数量遗传模型和二倍体性状数量基因（QTL）图构建方法相结合,导出双侧标记基因型下有关胚乳性状QTL的遗传组成、平均数和遗传方差分量,据之提出以某一区间双侧标记基因型胚乳性状的平均值为依变数,以该区间内任一点假定存在的QTL的加性效应d、显性效应h1和／或h2的系数为自变数,进行有重复观察值的多元线性回归分析,根据多元线性回归的显著性测验该点是否存在QTL,并估计出QTL的遗传效应。给定区间内任一点,皆可以此进行分析,从而可在整条染色体上作图,并以之确定QTL的数目和最可能位置,同时,在检测某一区间时,利用多元线性回归方法将该区间外可能存在的QTL的干扰进行统计控制,以提高QTL检测的精度。此外,还讨论了如何将之推广应用于其他类型的DNA不对应资料以及具复杂遗传模型的胚乳性状资料。     

Trophic level asynchrony in rates of phenological change for marine,freshwater and terrestrial environments

Recent changes in the seasonal timing (phenology) of familiar biological events have been one of the most conspicuous signs of climate change. However, the lack of a standardized approach to analysing change has hampered assessment of consistency in such changes among different taxa and trophic levels and across freshwater, terrestrial and marine environments. We present a standardized assessment of 25 532 rates of phenological change for 726 UK terrestrial, freshwater and marine taxa. The majority of spring and summer events have advanced, and more rapidly than previously documented. Such consistency is indicative of shared large scale drivers. Furthermore, average rates of change have accelerated in a way that is consistent with observed warming trends. Less coherent patterns in some groups of organisms point to the agency of more local scale processes and multiple drivers. For the first time we show a broad scale signal of differential phenological change among trophic levels; across environments advances in timing were slowest for secondary consumers, thus heightening the potential risk of temporal mismatch in key trophic interactions. If current patterns and rates of phenological change are indicative of future trends, future climate warming may exacerbate trophic mismatching, further disrupting the functioning, persistence and resilience of many ecosystems and having a major impact on ecosystem services.     

Fern species richness along a central Himalayan elevational gradient, Nepal

Aim The study explores fern species richness patterns along a central Himalayan elevational gradient (100–4800 m a.s.l.) and evaluates factors influencing the spatial increase and decrease of fern richness. Location The Himalayas stretch from west to east by 20°, i.e. 75–95° east, and Nepal is located from 80 to 88° east in this range. Methods We used published data of the distribution of ferns and fern allies to interpolate species elevational ranges. Defining species presence between upper and lower elevation limit is the basis for richness estimates. The richness pattern was regressed against the total number of rainy days, and gradients that are linearly related to elevation, such as length of the growing season, potential evapotranspiration (PET, energy), and a moisture index (MI = PET/mean annual rainfall). The regressions were performed by generalized linear models. Results A unimodal relationship between species richness and elevation was observed, with maximum species richness at 2000 m. Fern richness has a unimodal response along the energy gradients, and a linear response with moisture gradients. Main conclusions The study confirms the importance of moisture on fern distributions as the peak coincides spatially with climatic factors that enhance moisture levels; the maximum number of rainy days and the cloud zone. Energy‐related variables probably control species richness directly at higher elevations but at the lower end the effect is more probably related to moisture.