教育中的同伴效应研究述评：概念、模型与方法

教育中的同伴效应是指宿舍、班级、年级或学校内同伴的背景、行为及产出对学生产出或行为的影响。教育中的同伴效应起初使用的是同质性模型,即认为无论个体如何选择同伴,总效益是不变的,同伴效应是一种零和现象。进而发展到异质性模型,即认为同伴效应对不同个体的作用结果是不一样的,通过合理的分配能够提高总效益。研究方法则从以普通最小二乘法为主的统计关联研究,发展到借助于随机实验、自然实验以及准实验的因果推断研究。同伴效应的研究为正确地认识和评价相关教育政策,获得最优组织学校教学的方式,提高教学效率提供了依据。     

Brain Banks Spur New Frontiers in Neuropsychiatric Research and Strategies for Analysis and Validation

Neuropsychiatric disorders affect hundreds of millions of patients and families worldwide. To decode the molecular framework of these diseases, many studies use human postmortem brain samples. These studies reveal brain-specific genetic and epigenetic patterns via high-throughput sequencing technologies. Identifying best practices for the collection of postmortem brain samples, analyzing such large amounts of sequencing data, and interpreting these results are critical to advance neuropsychiatry. We provide an overview of human brain banks worldwide, including progress in China, highlighting some well-known projects using human postmortem brain samples to understand molecular regulation in both normal brains and those with neuropsychiatric disorders. Finally, we discuss future research strategies, as well as state-of-the-art statistical and experimental methods that are drawn upon brain bank resources to improve our understanding of the agents of neuropsychiatric disorders.     

The Precautionary Principle: Implications for Risk Management Strategies

The European Commission has published a Communication on the Precautionary Principle and a White Book on Governance. These provide us (as research civil servants of the Commission) an institutional framework for handling scientific information that is often incomplete, uncertain, and contested. But, although the Precautionary Principle is intuitively straightforward to understand, there is no agreed way of applying it to real decision-making. To meet this perceived need, researchers have proposed a vast number of taxonomies. These include ignorance auditing, type one-two-three errors, a combination of uncertainty and decision stakes through post-normal science and the plotting of ignorance of probabilities against ignorance of consequences. Any of these could be used to define a precautionary principle region inside a multidimensional space and to position an issue within that region. The rôle of anticipatory research is clearly critical but scientific input is only part of the picture. It is difficult to imagine an issue where the application of the Precautionary Principle would be non-contentious. From genetically-modified food to electro-smog, from climate change to hormone growth in meat, it is clear that: 1) risk and cost-benefit are only part of the picture; 2) there are ethical issues involved; 3) there is a plurality of interests and perspectives that are often in conflict; 4) there will be losers and winners whatever decision is made. Operationalisation of the Precautionary Principle must preserve transparency. Only in this way will the incommensurable costs and benefits associated with different stakeholders be registered. A typical decision will include the following sorts of considerations: 1) the commercial interests of companies and the communities that depend on them; 2) the worldviews of those who might want a greener, less consumerist society and/or who believe in the sanctity of human or animal life; 3) potential benefits such as enabling the world's poor to improve farming; 4) risks such as pollution, gene-flow, or the effects of climate change. In this paper we will discuss the use of a combination of methods on which we have worked and that we consider useful to frame the debate and facilitate the dialogue among stakeholders on where and how to apply the Precautionary Principle.     

Practical Murine Hematopathology: A Comparative Review and Implications for Research

Hematologic parameters are important markers of disease in human and veterinary medicine. Biomedical research has benefited from mouse models that recapitulate such disease, thus expanding knowledge of pathogenetic mechanisms and investigative therapies that translate across species. Mice in health have many notable hematologic differences from humans and other veterinary species, including smaller erythrocytes, higher percentage of circulating reticulocytes or polychromasia, lower peripheral blood neutrophil and higher peripheral blood and bone marrow lymphocyte percentages, variable leukocyte morphologies, physiologic splenic hematopoiesis and iron storage, and more numerous and shorter-lived erythrocytes and platelets. For accurate and complete hematologic analyses of disease and response to investigative therapeutic interventions, these differences and the unique features of murine hematopathology must be understood. Here we review murine hematology and hematopathology for practical application to translational investigation.Abbreviations: GEM, genetically engineered mouse; NMB, new methylene blue; nRBC, nucleated RBC; RDW, RBC distribution width; TNCC, total nucleated cell countHematology is an important adjunct to both clinical medicine and biomedical research, with more than 1700 currently funded NIH projects¹⁰⁹ and more than 3400 research articles published over the past 5 years using mouse models.¹²⁰ There are now more than 6000 genetically engineered mouse (GEM) models of disease, with 500 new GEM created each year at the Jackson Laboratory alone, and several large projects are underway to thoroughly phenotype each new mutant mouse strain (https://www.komp.org/).^13,176 A mouse tumor database (http://tumor.informatics.jax.org/mtbwi/index.do) is available to provide information regarding mouse models of human cancer, and the Mouse Phenome Database at the Jackson Laboratory provides links to phenotypic data for many GEM models (http://phenome.jax.org/).⁸ The defined components to complete the phenotyping of GEM models have been recently reviewed.^13,157,176 In addition, 21 inbred strains of mice are commonly used for investigations into such topics as response to infectious and genetically induced disease and dietary and pharmacologic therapies. These commonly used laboratory mouse strains have, for example, inherent differences in immunology or iron trafficking, which can affect research outcomes.^16,47,137 These interstrain differences are important to recognize and understand as a component of effective study design and prior to strain selection for laboratory investigations, especially when hematologic responses to disease need to be considered.^13,16,137For any appropriately designed experiment, concurrent age-, sex-, and strain-matched control mice must be included to accurately compare the effects of a disease, genetic manipulation or therapeutic intervention;^13,155 alternatively, individual mice can be used as their own controls in some studies. Several important guidelines exist to ensure that appropriate numbers of experimental and control mice are incorporated into a study design to maximize statistical power yet minimize waste.^{13,40-42,71,72,176} During and between studies, consistent blood collection methods are essential for accurate comparative analyses. Species-appropriate hematologic instrumentation and timely analysis of fresh blood are necessary to minimize preanalytic hematologic errors.^3,37,71 Especially important for mice and their restricted available blood volume are the use of practical, accurate, species-specific, and up-to-date hematologic methods.Here we comprehensively review murine hematology and hematopathologic responses to disease in the context of biomedical research, discovery, and phenotyping studies. To maximize the opportunity for detecting phenotypes, disease, and responses to therapeutic interventions in mice, we focus on providing a practical summary of methods and analysis for accurate hematologic studies and on describing the morphologic assessment of mouse hematopathology in peripheral blood and bone marrow in ways that will be useful to those—veterinarians and researchers alike—who work with murine species.     

The Impact of National Institutes of Health Funding on U.S. Cardiovascular Disease Research

Background

Intense interest surrounds the recent expansion of US National Institutes of Health (NIH) budgets as part of economic stimulus legislation. However, the relationship between NIH funding and cardiovascular disease research is poorly understood, making the likely impact of this policy change unclear.

Methods

The National Library of Medicine''s PubMed database was searched for articles published from 1996 to 2006, originating from U.S. institutions, and containing the phrases “cardiolog,” “cardiovascular,” or “cardiac,” in the first author''s department. Research methodology, journal of publication, journal impact factor, and receipt of NIH funding were recorded. Differences in means and trends were tested with t-tests and linear regression, respectively, with P≤0.05 for significance.

Results

Of 117,643 world cardiovascular articles, 36,684 (31.2%) originated from the U.S., of which 10,293 (28.1%) received NIH funding. The NIH funded 40.1% of U.S. basic science articles, 20.3% of overall clinical trials, 18.1% of randomized-controlled, and 12.2% of multicenter clinical trials. NIH-funded and total articles grew significantly (65 articles/year, P<0.001 and 218 articles/year, P<0.001, respectively). The proportion of articles receiving NIH funding was stable, but grew significantly for basic science and clinical trials (0.87%/year, P<0.001 and 0.67%/year, P = 0.029, respectively). NIH-funded articles had greater journal impact factors than non NIH-funded articles (5.76 vs. 3.71, P<0.001).

Conclusions

NIH influence on U.S. cardiovascular research expanded in the past decade, during the period of NIH budget doubling. A substantial fraction of research is now directly funded and thus likely sensitive to budget fluctuations, particularly in basic science research. NIH funding predicts greater journal impact.     

It Is Time to Re‐Evaluate the Peer Review Process for Preclinical Research

Problems in peer review, the backbone of maintaining high standards in scientific publishing, have led to wide spread discontent within the scientific community. Training in the peer review process and a simpler format to assist in decision making are possible courses to improve and expedite the process of peer review and scientific publishing.     

The Transformative Nature of Transparency in Research Funding

Central to research funding are grant proposals that researchers send in to potential funders for review, in the hope of approval. A survey of policies at major research funders found that there is room for more transparency in the process of grant review, which would strengthen the case for the efficiency of public spending on research. On that basis, debate was invited on which transparency measures should be implemented and how, with some concrete suggestions at hand. The present article adds to this discussion by providing further context from the literature, along with considerations on the effect size of the proposed measures. The article then explores the option of opening to the public key components of the process, makes the case for pilot projects in this area, and sketches out the potential that such measures might have to transform the research landscape in those areas in which they are implemented.     

Variation Thresholds for Extinction and Their Implications for Conservation Strategies

We examine the degree to which fitting simple dynamic models to time series of population counts can predict extinction probabilities. This is both an active branch of ecological theory and an important practical topic for resource managers. We introduce an approach that is complementary to recently developed techniques for estimating extinction risks (e.g., diffusion approximations) and, like them, requires only count data rather than the detailed ecological information available for traditional population viability analyses. Assuming process error, we use four different models of population growth to generate snapshots of population dynamics via time series of the lengths commonly available to ecologists. We then ask to what extent we can identify which of several broad classes of population dynamics is evident in the time series snapshot. Along the way, we introduce the idea of "variation thresholds," which are the maximum amount of process error that a population may withstand and still have a specified probability of surviving for a given length of time. We then show how these thresholds may be useful to both ecologists and resource managers, particularly when dealing with large numbers of poorly understood species, a common problem faced by those designing biodiversity reserves.     

Examining the Predictive Validity of NIH Peer Review Scores

The predictive validity of peer review at the National Institutes of Health (NIH) has not yet been demonstrated empirically. It might be assumed that the most efficient and expedient test of the predictive validity of NIH peer review would be an examination of the correlation between percentile scores from peer review and bibliometric indices of the publications produced from funded projects. The present study used a large dataset to examine the rationale for such a study, to determine if it would satisfy the requirements for a test of predictive validity. The results show significant restriction of range in the applications selected for funding. Furthermore, those few applications that are funded with slightly worse peer review scores are not selected at random or representative of other applications in the same range. The funding institutes also negotiate with applicants to address issues identified during peer review. Therefore, the peer review scores assigned to the submitted applications, especially for those few funded applications with slightly worse peer review scores, do not reflect the changed and improved projects that are eventually funded. In addition, citation metrics by themselves are not valid or appropriate measures of scientific impact. The use of bibliometric indices on their own to measure scientific impact would likely increase the inefficiencies and problems with replicability already largely attributed to the current over-emphasis on bibliometric indices. Therefore, retrospective analyses of the correlation between percentile scores from peer review and bibliometric indices of the publications resulting from funded grant applications are not valid tests of the predictive validity of peer review at the NIH.     

生化研究的策略与技术发展

生物化学是研究活细胞及有机体内各种分子及其相互间化学反应的科学,即研究生命的分子基础。细胞是生物体的基本结构和功能单位,机体的众多化学反应都在细胞内进行,所以生物化学又被定义为研究活细胞的化学组成及相互反应和进程的科学,即“生命的化学”,其实它涉及了细胞生物学、分子生物学和分子遗传学等几个大的学科领域。所以,生化研究的策略和技术发展对生命科学研究特别重要。由于有关生物医学科学的相互渗透以及生化与分子生物学技术的飞速进展,近两个世纪内（1780－1970年）生物化学的发展历经了从叙述生化进入功能或分子生化的阶段。在不久的将来,许多生命科学的关键问题将在分子机制和基因水平的基础上获得解决。     

Assay Strategies for the Discovery and Validation of Therapeutics Targeting Brugia pahangi Hsp90

The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target.     

Health Research Funding in Mexico: The Need for a Long-Term Agenda

Background

The legal framework and funding mechanisms of the national health research system were recently reformed in Mexico. A study of the resource allocation for health research is still missing. We identified the health research areas funded by the National Council on Science and Technology (CONACYT) and examined whether research funding has been aligned to national health problems.

Methods and Findings

We collected the information to create a database of research grant projects supported through the three main Sectoral Funds managed by CONACYT between 2003 and 2010. The health-related projects were identified and classified according to their methodological approach and research objective. A correlation analysis was carried out to evaluate the association between disease-specific funding and two indicators of disease burden. From 2003 to 2010, research grant funding increased by 32% at a compound annual growth rate of 3.5%. By research objective, the budget fluctuated annually resulting in modest increments or even decrements during the period under analysis. The basic science category received the largest share of funding (29%) while the less funded category was violence and accidents (1.4%). The number of deaths (ρ = 0.51; P<0.001) and disability-adjusted life years (DALYs; ρ = 0.33; P = 0.004) were weakly correlated with the funding for health research. Considering the two indicators, poisonings and infectious and parasitic diseases were among the most overfunded conditions. In contrast, congenital anomalies, road traffic accidents, cerebrovascular disease, and chronic obstructive pulmonary disease were the most underfunded conditions.

Conclusions

Although the health research funding has grown since the creation of CONACYT sectoral funds, the financial effort is still low in comparison to other Latin American countries with similar development. Furthermore, the great diversity of the funded topics compromises the efficacy of the investment. Better mechanisms of research priority-setting are required to adjust the research portfolio to the new health panorama of Mexican population.