The Scientific Impact of Developing Nations

This paper analyzes science productivity for nine developing countries. Results show that these nations are reducing their science gap, with R&D investments and scientific impact growing at more than double the rate of the developed world. But this “catching up” hides a very uneven picture among these nations, especially on what they are able to generate in terms of impact and output relative to their levels of investment and available resources. Moreover, unlike what one might expect, it is clear that the size of the nations and the relative scale of their R&D investments are not the key drivers of efficiency.     

基于机器学习的药物-靶标相互作用预测*

近年来,随着计算机硬件、软件工具和数据丰度的不断突破,以机器学习为代表的人工智能技术在生物、基础医学和药学等领域的应用不断拓展和融合,极大地推动了这些领域的发展,尤其是药物研发领域的变革。其中,药物-靶标相互作用(drug-target interactions, DTI)的识别是药物研发领域中的重要难题和人工智能技术交叉融合的热门方向,研究人员在DTI预测方面做了大量的工作,构建了许多重要的数据库,开发或拓展了各类机器学习算法和工具软件。对基于机器学习的DTI预测的基本流程进行了介绍,并对利用机器学习预测DTI的研究进行了回顾,同时对不同的机器学习方法运用于DTI预测的优缺点进行了简单总结,以期对开发更加有效的预测算法和DTI预测的发展提供帮助。     

Productivity and technical efficiency of suckler beef production systems: trends for the period 1990 to 2012

Over the past 23 years (1990 to 2012), French beef cattle farms have expanded in size and increased labour productivity by over 60%, chiefly, though not exclusively, through capital intensification (labour–capital substitution) and simplifying herd feeding practices (more concentrates used). The technical efficiency of beef sector production systems, as measured by the ratio of the volume value (in constant euros) of farm output excluding aids to volume of intermediate consumption, has fallen by nearly 20% while income per worker has held stable thanks to subsidies and the labour productivity gains made. This aggregate technical efficiency of beef cattle systems is positively correlated to feed self-sufficiency, which is in turn negatively correlated to farm and herd size. While volume of farm output per hectare of agricultural area has not changed, forage feed self-sufficiency decreased by 6 percentage points. The continual increase in farm size and labour productivity has come at a cost of lower production-system efficiency – a loss of technical efficiency that 20 years of genetic, technical, technological and knowledge-driven progress has barely managed to offset.     

Development of health biotechnology in developing countries: Can private-sector players be the prime movers?

Health biotechnology has rapidly become vital in helping healthcare systems meet the needs of the poor in developing countries. This key industry also generates revenue and creates employment opportunities in these countries. To successfully develop biotechnology industries in developing nations, it is critical to understand and improve the system of health innovation, as well as the role of each innovative sector and the linkages between the sectors. Countries' science and technology capacities can be strengthened only if there are non-linear linkages and strong interrelations among players throughout the innovation process; these relationships generate and transfer knowledge related to commercialization of the innovative health products. The private sector is one of the main actors in healthcare innovation, contributing significantly to the development of health biotechnology via knowledge, expertise, resources and relationships to translate basic research and development into new commercial products and innovative processes. The role of the private sector has been increasingly recognized and emphasized by governments, agencies and international organizations. Many partnerships between the public and private sector have been established to leverage the potential of the private sector to produce more affordable healthcare products. Several developing countries that have been actively involved in health biotechnology are becoming the main players in this industry. The aim of this paper is to discuss the role of the private sector in health biotechnology development and to study its impact on health and economic growth through case studies in South Korea, India and Brazil. The paper also discussed the approaches by which the private sector can improve the health and economic status of the poor.     

Critical appraisal of four IL-6 immunoassays

Background

Interleukin-6 (IL-6) contributes to numerous inflammatory, metabolic, and physiologic pathways of disease. We evaluated four IL-6 immunoassays in order to identify a reliable assay for studies of metabolic and physical function. Serial plasma samples from intravenous glucose tolerance tests (IVGTTs), with expected rises in IL-6 concentrations, were used to test the face validity of the various assays.

Methods and Findings

IVGTTs, administered to 14 subjects, were performed with a single infusion of glucose (0.3 g/kg body mass) at time zero, a single infusion of insulin (0.025 U/kg body mass) at 20 minutes, and frequent blood collection from time zero to 180 minutes for subsequent Il-6 measurement. The performance metrics of four IL-6 detection methods were compared: Meso Scale Discovery immunoassay (MSD), an Invitrogen Luminex bead-based multiplex panel (LX), an Invitrogen Ultrasensitive Luminex bead-based singleplex assay (ULX), and R&D High Sensitivity ELISA (R&D). IL-6 concentrations measured with MSD, R&D and ULX correlated with each other (Pearson Correlation Coefficients r = 0.47–0.94, p<0.0001) but only ULX correlated (r = 0.31, p = 0.0027) with Invitrogen Luminex. MSD, R&D, and ULX, but not LX, detected increases in IL-6 in response to glucose. All plasma samples were measurable by MSD, while 35%, 1%, and 4.3% of samples were out of range when measured by LX, ULX, and R&D, respectively. Based on representative data from the MSD assay, baseline plasma IL-6 (0.90±0.48 pg/mL) increased significantly as expected by 90 minutes (1.29±0.59 pg/mL, p = 0.049), and continued rising through 3 hours (4.25±3.67 pg/mL, p = 0.0048).

Conclusion

This study established the face validity of IL-6 measurement by MSD, R&D, and ULX but not LX, and the superiority of MSD with respect to dynamic range. Plasma IL-6 concentrations increase in response to glucose and insulin, consistent with both an early glucose-dependent response (detectable at 1–2 hours) and a late insulin-dependent response (detectable after 2 hours).     

抗体偶联药物国内研发现状及企业布局分析

抗体偶联药物(antibody-drug conjugates,ADC)由单克隆抗体和小分子细胞毒药物通过连接子偶联而成,因在血液瘤、实体瘤等临床治疗中被证明是一种极有前景的技术手段,已经成为国内外抗体药物研发的新热门方向.系统阐述了ADC药物开发及工业化生产中的核心五要素,对国内ADC的研发管线进行了梳理,并对参与A...     

Benefits of new tools in biotechnology to developing countries in south Asia: a perspective from UNESCO

South Asia, once considered as a laggard, has grown at about 6% on average over the past two decades and the current growth outlook is much brighter. However, this growth is not always well distributed and the challenges of institutionalising policies and mechanisms to ensure inclusive growth are now being seriously considered by these countries governments. The targets set by south Asian countries are primarily based on the investments in infrastructural sector with an objective to generate educated and skilled human resources. The other most important inclusive growth area is the core public services; Agriculture, Health, and Energy, which are increasingly becoming technology driven. Biotechnology has been increasingly seen now to be an area of technology that holds the greatest new potential to address problems arising from low productivity, overburdened health systems, high-cost unsustainable energy supplies and the need for developing new materials for industrial and environmental applications. This article attempts to highlight perspectives on some of the emerging areas of biotechnology that have good potential for economic development in the context of south Asia, as well as discuss briefly some of UNESCO's initiatives in biotechnology for that region.     

Benefits of new tools in biotechnology to developing countries in south Asia: A perspective from UNESCO

South Asia, once considered as a laggard, has grown at about 6% on average over the past two decades and the current growth outlook is much brighter. However, this growth is not always well distributed and the challenges of institutionalising policies and mechanisms to ensure inclusive growth are now being seriously considered by these countries governments.The targets set by south Asian countries are primarily based on the investments in infrastructural sector with an objective to generate educated and skilled human resources. The other most important inclusive growth area is the core public services; Agriculture, Health, and Energy, which are increasingly becoming technology driven. Biotechnology has been increasingly seen now to be an area of technology that holds the greatest new potential to address problems arising from low productivity, overburdened health systems, high-cost unsustainable energy supplies and the need for developing new materials for industrial and environmental applications.This article attempts to highlight perspectives on some of the emerging areas of biotechnology that have good potential for economic development in the context of south Asia, as well as discuss briefly some of UNESCO's initiatives in biotechnology for that region.     

Climate change,demographic pressures and global sustainability

This article emphasizes the need for broader approaches for formulating policies for mitigating the effects of climate change especially in the contexts of agricultural decisions, and population health and migration. Constraints imposed by rapid population growth in developing countries for achievement of Sustainable Development Goals are discussed and evidence is presented on “unwanted” fertility from India. Second, comparisons are made for India during 2002–2016 for average well depths in 495 districts and terrestrial water storage anomalies assessed via GRACE satellites for 274 1° × 1° grids using estimated parameters from dynamic random effects models. Lastly, migration patterns especially of the highly educated from 39 sending countries to OECD countries during 2000–2010 are analyzed using dynamic random effects models and total fertility rates were significantly associated with higher migration rates for the highly educated. Implications of the empirical evidence for enhancing global sustainability are discussed.     

The Characteristics and Trends of Socioeconomic Metabolism in China

China has become the country with the largest resource use and has high levels of waste emissions that pose a great management challenge. To provide more details about environmental problems and to find effective solutions, this article analyzed the scale, structure, and trend of the socioeconomic metabolism in China during the period 1992–2014 based on economy‐wide material flow accounts (EW‐MFA), and predicted resource use during the period of the 13th Five‐Year Plan. The results of this study show that the scale of China's socioeconomic metabolism in China increased more than twofold, during 1992–2014. However, after 2011, with the economic slowdown, the growth rates of total material requirement (TMR), direct material input (DMI), and domestic processed output (DPO) began to decrease. China may reach an inflection point, but this point will probably not be approached before the year 2020. Material recycling (MR) has played an important role in improving resource productivity, improving it by 92.52 renminbi per tonne in 2014. Metallic minerals and fossil fuels are the main sources of hidden flow. Carbon dioxide (CO₂) emissions, construction waste, and agricultural emissions have become the major sources of DPO. Because of the 13th Five‐Year Plan, China may slow the growth rate of DMI and may save 10.26 gigatonnes of resources during 2015–2020. Resource productivity is predicted to increase by 15.91%. Imports and MR may play more important roles. These suggestions are made: (1) strengthening the recycling system; (2) stronger policies, especially in metallic mineral and fossil fuels; (3) developing management systems for CO₂ emissions, construction waste, and agricultural emissions; and (4) adjusting China's economic structure.     

Factors affecting the work productivity of Oraon agricultural laborers of Jalpaiguri district, West Bengal

In developing countries like India, where the incidence of protein-calorie malnutrition is high and mechanization is at a minimum, human labor provides much of the power for physical activity. This study presents anthropometric measurements, somatotypes, food intakes, energy expenditures, and work outputs of Oraon agricultural laborers of the Jalpaiguri district, West Bengal, in an attempt to identify the factors that predict high work productivity. Specifically, this study investigates 1) the relationship between morphological variation (anthropometric measurements and somatotype) and work productivity, 2) the nature and extent of the relationship between nutritional status and work productivity, and 3) the best predictor variables of work output. Classification of groups on the basis of median values of work output show that in the aggregate, the high productive groups are significantly younger than low-productive groups in both sexes. Before age-adjustment, the high productive groups show higher mean values of a few body dimensions, though these differ by sex, and both males and females exhibit a normal range of blood pressure and pulse rate values. Mean values of grip strength and back strength are higher in high-output men and women. Mean values of both food intake and energy expenditure are also higher among men in high-output groups, with only food intake higher in high-output women. However, after eliminating the effects of age, the differences between low-productive groups and high-productive groups in most of the variables are not significant. Productivity predictors in males consist of age, food intake and chest girth (inhalation). Females, on the other hand, show age and grip strength (left) as work output predictors.     

Genetically modified and organic crops in developing countries: A review of options for food security

Since two decades ago, when the first GM crops were introduced, there have increasingly been hot debates on the applications of gene manipulation. Currently, the development of GM crop varieties has raised a wide range of new legal, ethical and economic questions in agriculture. There is a growing body of literature reflecting the socio-economic and environmental impacts of GM crops which aims to criticize their value for farming systems. While organic crops are promoted as environmentally-friendly products in developed countries, they have provoked great controversy in developing countries facing food security and a low agricultural productivity. Discussion has been especially vigorous when organic farming was introduced as an alternative method. There are in fact, a few tradeoffs in developing countries. On the one hand, farmers are encouraged to accept and implement GM crops because of their higher productivity, while on the other hand, organic farming is encouraged because of socio-economic and environmental considerations. A crucial question facing such countries is therefore, whether GM crops can co-exist with organic farming. This paper aims to review the main considerations and tradeoffs.     

When Quality Beats Quantity: Decision Theory,Drug Discovery,and the Reproducibility Crisis

A striking contrast runs through the last 60 years of biopharmaceutical discovery, research, and development. Huge scientific and technological gains should have increased the quality of academic science and raised industrial R&D efficiency. However, academia faces a "reproducibility crisis"; inflation-adjusted industrial R&D costs per novel drug increased nearly 100 fold between 1950 and 2010; and drugs are more likely to fail in clinical development today than in the 1970s. The contrast is explicable only if powerful headwinds reversed the gains and/or if many "gains" have proved illusory. However, discussions of reproducibility and R&D productivity rarely address this point explicitly. The main objectives of the primary research in this paper are: (a) to provide quantitatively and historically plausible explanations of the contrast; and (b) identify factors to which R&D efficiency is sensitive. We present a quantitative decision-theoretic model of the R&D process. The model represents therapeutic candidates (e.g., putative drug targets, molecules in a screening library, etc.) within a “measurement space", with candidates'' positions determined by their performance on a variety of assays (e.g., binding affinity, toxicity, in vivo efficacy, etc.) whose results correlate to a greater or lesser degree. We apply decision rules to segment the space, and assess the probability of correct R&D decisions. We find that when searching for rare positives (e.g., candidates that will successfully complete clinical development), changes in the predictive validity of screening and disease models that many people working in drug discovery would regard as small and/or unknowable (i.e., an 0.1 absolute change in correlation coefficient between model output and clinical outcomes in man) can offset large (e.g., 10 fold, even 100 fold) changes in models’ brute-force efficiency. We also show how validity and reproducibility correlate across a population of simulated screening and disease models. We hypothesize that screening and disease models with high predictive validity are more likely to yield good answers and good treatments, so tend to render themselves and their diseases academically and commercially redundant. Perhaps there has also been too much enthusiasm for reductionist molecular models which have insufficient predictive validity. Thus we hypothesize that the average predictive validity of the stock of academically and industrially "interesting" screening and disease models has declined over time, with even small falls able to offset large gains in scientific knowledge and brute-force efficiency. The rate of creation of valid screening and disease models may be the major constraint on R&D productivity.     

GM crops in Ethiopia: a realistic way to increase agricultural performance?

Much has been published on the application of genetically modified (GM) crops in Africa, but agricultural performance has hardly been addressed. This paper discusses the main consequences of GM crops on agricultural performance in Ethiopia. Three main criteria of performance - productivity, equitability and sustainability - are evaluated in the context of the Ethiopian agricultural sector. We conclude that the application of GM crops can improve the agricultural productivity and sustainability, whereas equitability cannot be stimulated and might even exacerbate the gap between socioeconomic classes. Before introducing GM crops to Ethiopian agriculture, regulatory issues should be addressed, public research should be fostered, and more ex ante values and socioeconomic studies should be included.     

Fostering molecular breeding in developing countries

Molecular breeding (MB) increases genetic gain per crop cycle, stacks favourable alleles at target loci and reduces the number of selection cycles. In the last decade, the private sector has benefitted immensely from MB, which demonstrates its efficacy. In contrast, MB adoption is still limited in the public sector, and it is hardly used in developing countries. Major bottlenecks in these countries include shortage of well-trained personnel, inadequate high-throughput capacity, poor phenotyping infrastructure, lack of information systems or adapted analysis tools or simply resource-limited breeding programmes. The emerging virtual platforms aided by the information and communication technology revolution will help to overcome some of these limitations by providing breeders with better access to genomic resources, advanced laboratory services and robust analytical and data management tools. Apart from some advanced national agricultural research systems (NARS), the implementation of large-scale molecular breeding programmes in developing countries will take time. However, the exponential development of genomic resources, including for less-studied crops, the ever-decreasing cost of marker technologies and the emergence of platforms for accessing MB tools and support services, plus the increasing public–private partnerships and needs-driven demand for improved varieties to counter the global food crisis, are all grounds to predict that MB will have a significant impact on crop breeding in developing countries. These predictions are supported by some preliminary successful examples presented in this paper.     

Determinants of the Pace of Global Innovation in Energy Technologies

Understanding the factors driving innovation in energy technologies is of critical importance to mitigating climate change and addressing other energy-related global challenges. Low levels of innovation, measured in terms of energy patent filings, were noted in the 1980s and 90s as an issue of concern and were attributed to limited investment in public and private research and development (R&D). Here we build a comprehensive global database of energy patents covering the period 1970–2009, which is unique in its temporal and geographical scope. Analysis of the data reveals a recent, marked departure from historical trends. A sharp increase in rates of patenting has occurred over the last decade, particularly in renewable technologies, despite continued low levels of R&D funding. To solve the puzzle of fast innovation despite modest R&D increases, we develop a model that explains the nonlinear response observed in the empirical data of technological innovation to various types of investment. The model reveals a regular relationship between patents, R&D funding, and growing markets across technologies, and accurately predicts patenting rates at different stages of technological maturity and market development. We show quantitatively how growing markets have formed a vital complement to public R&D in driving innovative activity. These two forms of investment have each leveraged the effect of the other in driving patenting trends over long periods of time.     

The Brazilian vaccine manufacturers' perspective and its current status

This article aims to give an overview of the current situation and perspectives for the Brazilian vaccine manufacturers, who play strong roles for developing countries in this field.The research, development and production of immunobiologicals in Brazil, especially vaccines for human use, is mainly supported by governmental institutions linked to the Ministry of Health as part of a strategy that prioritizes the public sector for access to vaccines and other biologicals that are regarded essential for the population.As a result, 83% of the vaccines required in 2007 were provided by national vaccine producers and only 17% were imported, mainly to reference centers for special vaccines that were used for special patients. Moreover, the country has actively exported yellow fever vaccine since 2002 and meningitis AC vaccine since 2007, having covered more than 60 nations.The perspectives have positively increased due to the government's policy of making internal investments, not only to avoid the external dependence of products for public health, but also to strengthen the Brazilian industrial sector related to biotechnology.     

Reviewing Dengue: Still a Neglected Tropical Disease?

Dengue is currently listed as a “neglected tropical disease” (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003–2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.     

An intellectual property sharing initiative in agricultural biotechnology: development of broadly accessible technologies for plant transformation

The Public Intellectual Property Resource for Agriculture (PIPRA) was founded in 2004 by the Rockefeller Foundation in response to concerns that public investments in agricultural biotechnology benefiting developing countries were facing delays, high transaction costs and lack of access to important technologies due to intellectual property right (IPR) issues. From its inception, PIPRA has worked broadly to support a wide range of research in the public sector, in specialty and minor acreage crops as well as crops important to food security in developing countries. In this paper, we review PIPRA's work, discussing the failures, successes, and lessons learned during its years of operation. To address public sector's limited freedom-to-operate, or legal access to third-party rights, in the area of plant transformation, we describe PIPRA's patent 'pool' approach to develop open-access technologies for plant transformation which consolidate patent and tangible property rights in marker-free vector systems. The plant transformation system has been licensed and deployed for both commercial and humanitarian applications in the United States (US) and Africa, respectively.