Strategic emphases for tropical diseases research: a TDR perspective

Setting priorities for health research is a difficult task, especially for the neglected diseases of the poor. A new approach to priority setting for tropical diseases research has been adopted by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (known as the TDR). Priorities are defined on the basis of a comprehensive analysis of research needs and research opportunities for each of the ten major tropical diseases in the TDR portfolio. The resulting strategic emphases matrix reflects the priorities for tropical diseases research from the perspective of the TDR. Its purpose is not to impose global research priorities, but we believe the results could be useful to other organizations.     

Preventive chemotherapy as a strategy for elimination of neglected tropical parasitic diseases: endgame challenges

Global efforts to address neglected tropical diseases (NTDs) were stimulated in January 2012 by the London declaration at which 22 partners, including the Bill & Melinda Gates Foundation, World Bank, World Health Organization (WHO) and major pharmaceutical companies committed to sustaining and expanding NTD programmes to eliminate or eradicate 11 NTDs by 2020 to achieve the goals outlined in the recently published WHO road map. Here, we present the current context of preventive chemotherapy for some NTDs, and discuss the problems faced by programmes as they consider the ‘endgame’, such as difficulties of access to populations in post-conflict settings, limited human and financial resources, and the need to expand access to clean water and improved sanitation for schistosomiasis and soil-transmitted helminthiasis. In the case of onchocerciasis and lymphatic filariasis, ivermectin treatment carries a significant risk owing to serious adverse effects in some patients co-infected with the tropical eye worm Loa loa filariasis. We discuss the challenges of managing complex partnerships, and maintain advocacy messages for the continued support for elimination of these preventable diseases.     

Tobacco-related disease burden and preventive initiatives in China. Global health and the chronic diseases: perspective, policy and practice

The burden of chronic diseases in global health is a surging area of research. The Global Health Initiative at the National Heart, Lung, and Blood Institute brings together investigators from developing countries with those from the developed world to study these diseases. In China, approximately 83 percent of all deaths in 2000 were attributed to chronic illnesses, which are the research focuses of the Chinese center of the Global Health Initiative. Tobacco use as well as passive smoking are modifiable risk factors in a large number of such chronic conditions. The prevalence of smoking in China is extensive and has inseparable ties to the economy, with tobacco taxes making up a large portion of government revenue in poorer provinces. Methods of smoking prevention have been piloted in some Chinese schools, which have mitigated the increase in smoking rate but have not resulted in a primary preventive effect. Efforts by the Yale Global Health Initiative and the Yale-China Association are bringing researchers together to address chronic disease in China as Yale School of Medicine enters its 200th year.     

Lessons for collaborative research in a changing operating environment

This Comment records the details of an unusual multipartner ecological research programme studying Temperate Highland Peat Swamps on Sandstone in the Sydney Basin‐Blue Mountains area of New South Wales. We draw lessons from the experience of designing and managing this multipartner ecological programme, which was based on a nontraditional funding source – that is an enforceable undertaking required of a coal mining company related to an occurrence at a mine site. The research programme encompassed geomorphology, ecohydrology and ecology of a number of sites. Given the currently constrained public‐good environmental research funding and pressures for both researchers and managers to find new, collaborative ways of funding and implementing research, lessons drawn from such innovative experiences may be of wider utility. In particular, lessons are drawn from the programme regarding the time required to design collaborative processes and the need for explicit programme management capacities.     

NTD Health: An electronic medical record system for neglected tropical diseases

Introduction: The use of technological resources to support processes in health systems has generated robust, interoperable, and dynamic platforms. In the case of institutions working with neglected tropical diseases, there is a need for specific customizations of these diseases.Objectives: To establish a medical record platform specialized in neglected tropical diseases which could facilitate the analysis of treatment evolution in patients, as well as generate more accurate data about various clinical aspects.Materials and methods: A set of requirements to develop state of the art forms, concepts, and functionalities to include neglected tropical diseases were compiled. An OpenMRS distribution (version 2.3) was used as reference to build the platform, following the recommended guidelines and shared-community modules.Results: All the customized information was developed in a platform called NTD Health, which is web-based and can be upgraded and improved by users without technological barriers.Conclusions: The electronic medical record system can become a useful tool for other institutions to improve their health practices as well as the quality of life for neglected tropical disease patients, simplifying the customization of healthcare systems able to interoperate with other platforms.     

Access to data and material for research: putting empirical evidence into perspective

The aim of this article is to put into critical perspective the empirical findings on secrecy and withholding in research. In other words, by taking existing empirical literature into account, it is intended that a crucial question is answered: Is secrecy and withholding in research harmful or innocuous to science? To understand how secrecy and withholding in research have affected academic science, empirical studies have been placed in the wider context of Mertonian underpinnings of the anticommons threat. The turning point in testing the effects of secrecy and withholding of data and material on scientific research was marked by statistical studies based on surveys and bibliometric measures. These two types of empirical studies have given answers to the basic question since academia was threatened by different modes of practicing science.     

Cell death pathology: perspective for human diseases

Apoptosis, a genetically regulated form of cell death with distinct biochemical and morphological features, plays a relevant physiological and pathological role in the organism, being pivotal in the maintenance of tissue development and homeostasis in the adult as well as in the regulation of immune responses. Deregulation of this process causes several human disorders including cancer, autoimmune and neurodegenerative diseases. Thus, modulation of the apoptotic process and of cell death in general, is a potential therapeutic approach for the treatment of several human pathologies.     

区域生态系统健康评价——研究方法与进展

生态系统健康评价是当前宏观生态学与生态系统管理研究的热点问题之一,区域尺度的生态系统健康评价则是生态系统健康评价研究的一个重要发展方向。在探讨生态系统健康时空尺度特征的基础上,明确界定了区域生态系统健康及其评价等相关概念,结合目前区域尺度生态系统健康评价的相关研究进展,从评价的区域类型、目标单元、模型方法、指标选取及其阈值、权重设定等方面探讨了区域生态系统健康评价的基本原理与方法,并展望了进一步研究的重点方向,即评价结果的多尺度综合与尺度转换、景观生态学理论与方法的应用、3S技术的综合应用等理论与技术问题。     

Evaluation for regional ecosystem health: methodology and research progress

The evaluation for ecosystem health is one of the hotspots in the fields of macro-ecology and ecosystem management. Conducting analysis at the regional scale is an important direction for evaluating ecosystem health. Changing the spatial scale from the local to the regional level leads to great differences in targets and methodologies for ecosystem health evaluation and creates a new direction for regional ecosystem health research. Compared with the ecosystem health at the local scale, which refers to a single ecosystem type, the regional ecosystem health focuses on the health conditions and spatial patterns of different ecosystem types. However, there has been little attention paid to this very research up to now. Based on the progress on ecosystem health studies at the regional scale, the study reported in this article aims to discuss the implications of the conception of regional ecosystem health and to put forward a methodology for evaluating the regional ecosystem health. The main results include: (1) there is a significant scaling effect on the ecosystem health analysis, and the regional level is the key scale used to focus on the correlation between spatially neighboring ecosystems in terms of ecosystem health; (2) regional ecosystem health can be defined through 4 aspects, i.e., vigor, organization, resilience, and ecosystem service functions; (3) the basic evaluation objects of the regional ecosystem health is spatial entity, which is the matrix of different ecosystem types; (4) indicator system method is the only approach to evaluate regional ecosystem health; (5) the absolute thresholds of the evaluation indicators for the regional ecosystem health do not exist; the aim of the evaluation is to discuss the temporal dynamic changes and spatial differences of health conditions rather than to ascertain whether a region is healthy or not in view of ecological sustainability; and (6) the integration of evaluation results at multispatial scales, the application of this methodology in the landscape ecology, and the utilization of geographic information systems (GIS), remote sensing (RS), and Global Positioning Systems (GPS) technologies are the main directions for further research.     

Collegiality and careerism trump critical questions and bold new ideas: a student's perspective and solution. The structure of scientific funding limits bold new ideas

Funding agencies (and journals) seem to be discriminating against ideas that are contrary to the mainstream, leading to leading to the preferential funding of predictable and safe research over radically new ideas. To remedy this problem a restructuring of the scientific funding system is needed, e.g. by utilizing laymen--together with scientists--to evaluate grant proposals.     

Gene transfer to the vasculature: historical perspective and implication for future research objectives

Cardiovascular diseases are a major cause of fatality, disability, and economic burden in Western civilization. Although the pharmaceutical industry has delivered a plethora of drugs for treatment of diverse cardiovascular complaints, there remain many conditions for which pharmacological regimens are either nonexistent or largely ineffective. In contrast, remarkable progress has been made in the field of vascular gene transfer in the last decade. The vast majority of studies are preclinical, although a number of high profile vascular gene therapy clinical trials are in progress. In principle, vascular gene therapy represents an unprecedented opportunity to treat a host of cardiovascular diseases in humans although many scientific, clinical, and ethical obstacles remain. Here we discuss the rapid progress in preclinical vascular gene therapy, highlight the most appropriate gene delivery vectors, and discuss the advances toward the ultimate goal of an efficient and safe gene therapy for diverse cardiovascular diseases.     

Measuring and improving the quality of mental health care: a global perspective

Mental disorders are common worldwide, yet the quality of care for these disorders has not increased to the same extent as that for physical conditions. In this paper, we present a framework for promoting quality measurement as a tool for improving quality of mental health care. We identify key barriers to this effort, including lack of standardized information technology‐based data sources, limited scientific evidence for mental health quality measures, lack of provider training and support, and cultural barriers to integrating mental health care within general health environments. We describe several innovations that are underway worldwide which can mitigate these barriers. Based on these experiences, we offer several recommendations for improving quality of mental health care. Health care payers and providers will need a portfolio of validated measures of patient‐centered outcomes across a spectrum of conditions. Common data elements will have to be developed and embedded within existing electronic health records and other information technology tools. Mental health outcomes will need to be assessed more routinely, and measurement‐based care should become part of the overall culture of the mental health care system. Health care systems will need a valid way to stratify quality measures, in order to address potential gaps among subpopulations and identify groups in most need of quality improvement. Much more attention should be devoted to workforce training in and capacity for quality improvement. The field of mental health quality improvement is a team sport, requiring coordination across different providers, involvement of consumer advocates, and leveraging of resources and incentives from health care payers and systems.     

Taking advantage of physiological proteolytic processing of the prion protein for a therapeutic perspective in prion and Alzheimer diseases

Prion and Alzheimer diseases are fatal neurodegenerative diseases caused by misfolding and aggregation of the cellular prion protein (PrP^C) and the β-amyloid peptide, respectively. Soluble oligomeric species rather than large aggregates are now believed to be neurotoxic. PrP^C undergoes three proteolytic cleavages as part of its natural life cycle, α-cleavage, β-cleavage, and ectodomain shedding. Recent evidences demonstrate that the resulting secreted PrP^C molecules might represent natural inhibitors against soluble toxic species. In this mini-review, we summarize recent observations suggesting the potential benefit of using PrP^C-derived molecules as therapeutic agents in prion and Alzheimer diseases.     

Priorities for mental health research in Europe: A survey among national stakeholders' associations within the ROAMER project

Within the ROAMER project, funded by the European Commission, a survey was conducted with national associations/organizations of psychiatrists, other mental health professionals, users and/or carers, and psychiatric trainees in the 27 countries of the European Union, aiming to explore their views about priorities for mental health research in Europe. One hundred and eight associations/organizations returned the questionnaire. The five most frequently selected research priorities were early detection and management of mental disorders, quality of mental health services, prevention of mental disorders, rehabilitation and social inclusion, and new medications for mental disorders. All these areas, except the last one, were among the top ten research priorities according to all categories of stakeholders, along with stigma and discrimination. These results seem to support the recent argument that some rebalancing in favor of psychosocial and health service studies may be needed in psychiatric research.     

Whole-genome sequencing as a first-tier diagnostic framework for rare genetic diseases

Rare diseases affect nearly 300 million people globally with most patients aged five or less. Traditional diagnostic approaches have provided much of the diagnosis; however, there are limitations. For instance, simply inadequate and untimely diagnosis adversely affects both the patient and their families. This review advocates the use of whole genome sequencing in clinical settings for diagnosis of rare genetic diseases by showcasing five case studies. These examples specifically describe the utilization of whole genome sequencing, which helped in providing relief to patients via correct diagnosis followed by use of precision medicine.     

Stem cells in development of therapeutics for Parkinson's disease: a perspective

Using Parkinson's disease as a prototype of neurodegenerative diseases, we propose applications of human stem cells in the development of therapeutics for neurodegenerative diseases. First, in vitro differentiation of human stem cells offers a versatile model for dissecting molecular interactions underlying human dopamine (DA) neuron specification, which may form a foundation for instigating regeneration of DA neurons from progenitors that reside in the brain. Second, stem cells derived from diseased cells or through genetic modification can serve as a platform for unraveling biochemical processes that lead to the cellular pathogenesis of degeneration. This may in turn serve as a template for identifying or developing therapeutics for slowing, stopping, or reversing the disease process. And finally, stem cells, particularly those induced from patients' own cells, provide a reliable source of DA neurons for cell-based therapy.     

An ironic reductio for a 'pro-life' argument: Hurlbut's proposal for stem cell research

William Hurlbut, a Stanford University bioethicist and member of the President's Council on Bioethics, recently proposed a solution to the current impasse over human embryonic stem cell research in the United States. He suggested that researchers could use genetic engineering and somatic cell nuclear transfer (i.e. cloning) to develop human 'pseudo-embryos' that have no potential to develop fully into human persons. According to Hurlbut, even thinkers who typically ascribe high moral status to human embryos could approve of destroying these 'pseudo-embryos' for the sake of harvesting human embryonic stem cells. This essay argues, first, that an argument based on the 'paradox of the heap' (an argument that many 'pro-life' thinkers employ in order to defend the notion that human embryos have high moral value from the moment of conception) challenges the ethical legitimacy of Hurlbut's proposal. Second, the paper argues that this conflict may illustrate a reductio ad absurdum for this 'pro-life' argument itself rather than being a problem for Hurlbut's proposal. As a result, the paper challenges the 'pro-life'strategy of arguing that one should respond to uncertainty about the moral status of developing embryos by being morally 'cautious' and granting all human embryos full moral status from the moment of conception. It appears that one is faced with a complex series of choices (about where to draw the moral line between entities that are human persons and entities that are not), and a strict moral 'cautiousness' about this series of choices may ultimately lead to absurdity.